Journal

Computational and Mathematical Methods in Medicine

Papers (46)

PTGIS May Be a Predictive Marker for Ovarian Cancer by Regulating Fatty Acid Metabolism

Background. Ovarian cancer tends to metastasize to the omentum, which is an organ mainly composed of adipose tissue. Many studies have found that fatty acid metabolism is related to the occurrence and metastasis of cancers. Therefore, it is possible that fatty acid metabolism‐related genes (FAMRG) affect the prognosis of ovarian cancer patients. Methods. First, profiles of ovarian cancer and normal ovarian tissue transcriptomes were acquired from The Cancer Genome Atlas (TCGA) and the Genotype‐Tissue Expression (GTEx) databases. A LASSO regression predictive model was developed via the “glmnet” R package. The nomogram was created via the “regplot.” Gene Set Variation Analysis (GSVA), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology (GO) analyses were conducted to determine the FAMRGs’ roles. The percentage of immunocyte infiltration was calculated via CIBERSORT. Using “pRRophetic,” the sensitivity of eight regularly used medications and immunotherapy was anticipated. Results. 125 genes were determined as different expression genes (DEGs). Based on RXRA, ECI2, PTGIS, and ACACB, a prognostic model is created and the risk score is calculated. Analyses of univariate and multivariate regressions revealed that the risk score was a distinct prognostic factor (univariate: HR: 2.855, 95% CI: 1.756‐4.739, P < 0.001; multivariate: HR: 2.943, 95% CI: 1.800‐4.812, P < 0.001). The nomogram demonstrated that it properly predicted the 1‐year survival rate. The expression of memory B molecular units, follicular helper T molecular units, regulatory T molecular units, and M1 macrophages differed remarkably between the groups at high and low risk (P < 0.05). Adipocytokine signaling pathways, cancer pathways, and degradation of valine, leucine, and isoleucine vary between high‐ and low‐risk populations. The findings of the GO enrichment revealed that the extracellular matrix and cellular structure were the two most enriched pathways. PTGIS, which is an important gene in fatty acid metabolism, was identified as the hub gene. This result was verified in ovarian cancer and ovarian tissues. The connection between the gene and survival was statistically remarkable (P = 0.015). The pRRophetic algorithm revealed that the low‐risk group was more adaptable to cisplatin, doxorubicin, 5‐fluorouracil, and etoposide (P < 0.001). Conclusion. PTGIS may be an indicator of prognosis and a possible therapeutic target for the therapy of ovarian cancer patients. The fatty acid metabolism of immune cells may be controlled, which has an indirect effect on cancer cell growth.

Effects of Quantitative Nursing Combined with Psychological Intervention in Operating Room on Stress Response, Psychological State, and Prognosis of Patients Undergoing Laparoscopic Endometrial Cancer Surgery

Objective. To investigate the effects of quantitative nursing and psychological interventions on stress response, mental health, and prognosis in endometrial cancer patients having laparoscopic surgery. Methods. The random number table approach was used to identify and split 98 patients with endometrial cancer undergoing laparoscopic surgery at our hospital’s Obstetrics and Gynecology Hospital ( n = 49 ) into observation and control groups ( n = 49 ) from May 2020 to February 2022. Both groups received standard care in the operating room, while those in the observation group received quantitative and psychological interventions in the operating room. Both groups were compared for perioperative markers, stress indicators, coping strategies, and pain levels. Results. In terms of age, TNM stage, or pathology, there was no statistically significant difference between the two groups ( P > 0.05 ). Both the observation and control groups experienced statistically significant ( P < 0.05 ) reductions in the perioperative markers of operation time, intraoperative blood loss, and overall hospital stay. Both groups’ SAS and SDS scores were lower than they had been prior to surgery, but the observation group had lower scores than the control group, and these differences were statistically significant ( P < 0.05 ). Postsurgery, the observation group’s cortisol and adrenaline levels were lower than those of the control group, and both groups’ levels were higher than before surgery, with statistical significance ( P < 0.05 ) in both groups. Neither coping style nor pain level differed significantly between the two groups before surgery ( P > 0.05 ). Postoperatively, while yield item scores were lower and faces scores were higher than the control group, the observation group’s avoidance item score was lower than the control group. All with statistical significance. There were substantial differences in NRS SCORE between observers and controls. Conclusion. After laparoscopic surgery to remove endometrial cancer, patients may benefit from the combination of quantitative nursing and psychological intervention in the operating room to alleviate postoperative anxiety and sadness and reduce stress reaction.

Prognosis and Efficacy of Laparoscopic Surgery on Patients with Endometrial Carcinoma: Systematic Evaluation and Meta-Analysis

Objective. The prognosis and efficacy of laparoscopic surgery (LPS) and open surgery or robotic surgery (RS) on endometrial carcinoma (EC) patients were compared. Methods. Data as of May 2021 were retrieved from databases like PubMed, Embase, Cochrane Library, and Web of Science. The study involved randomized controlled trials (RCTs), cohort studies, or case-control studies for comparing the effects of LPS and open surgery or robotic surgery (RS) on EC treatment. The primary outcomes included duration of operation, blood loss, length of stay (LOS), postoperative complications, and recurrence rate. Secondary outcomes included 3-year progression-free survival (PFS) rate/disease-free survival (DFS) rate and 3-year overall survival (OS) rate. Results. A total of 24 studies were involved, and all of them were cohort studies except 1 RCT and 1 case-control study. There was no significant difference in duration of operation between LPS and open surgery ( MD = − 0.06 , 95% CI: -0.37 to 0.25) or RS ( MD = − 0.15 , 95% CI: -1.27 to 0.96). In comparison with the open surgery, LPS remarkably reduced blood loss ( MD = − 0.43 , 95% CI: -0.58 to -0.29), LOS ( MD = − 0.71 , 95% CI: -0.92 to -0.50), and the complication occurrence rate ( RR = 0.83 , 95% CI: 0.73 to 0.95). However, LPS and RS saw no difference in blood loss ( MD = 0.01 , 95% CI: -0.77 to 0.79). Besides, in comparison with RS, LPS prominently shortened the LOS ( MD = 0.26 , 95% CI: 0.12 to 0.40) but increased the complication occurrence rate ( RR = 1.74 , 95% CI: 1.57 to 1.92). In contrast to open surgery or RS, LPS saw no difference in occurrence rate ( RR = 0.75 , 95% CI: 0.56 to 1.01; RR = 0.97 , 95% CI: 0.62 to 1.53), 3-year PFS/DFS ( RR = 0.99 , 95% CI: 0.90 to 1.09; RR = 1.30 , 95% CI: 0.87 to 1.96), and 3-year OS ( RR = 0.97 , 95% CI: 0.91 to 1.04; RR = 1.21 , 95% CI: 0.91 to 1.60). Conclusion. In sum, LPS was better than open surgery, which manifested in the aspects of less blood loss, shorter LOS, and fewer complications. LPS, therefore, was the most suitable option for EC patients. Nevertheless, LPS had no advantage over RS, and sufficient prospective RCTs are needed to further confirm its strengths.

Clinical Application of Digital 3D Reconstruction and 3D Printing Technology in Endometrial Cancer (EC) Surgery

Aims. We use CTA and magnetic resonance data to use digital three-dimensional reconstruction and 3D printing technology to reproduce the solid replication of the uterus and surrounding tissues in vitro, fully evaluate the adjacency of tumor tissues with surrounding important organs, blood vessels, and lymph nodes, and reduce the impact. The normal organ structure and function of the surgeon can shorten the operation time, reduce the bleeding during the operation, and reduce the perioperative complications of the patient to improve the prognosis of the patient. Materials and Methods. Select 40 EC patients and divide them into group A (3D reconstruction data is transmitted to 3D printing equipment according to the results of CTA and MRI examination, and a 3D model is printed out according to the ratio of 1 : 1 for evaluation and judgment before surgery) and group B (according to MRI imaging examination, there were 20 cases each). Different surgical conditions, quality of life, adverse reactions, and clinical efficacy were evaluated in each group. Results. The operation time, the time of the first anus exhaust, the hospitalization time after the operation, and the blood loss of the operation in group A were significantly lower than those in group B. Statistics showed that the difference was significant ( P < 0.05 ). The quality of life scores of emotion, cognition, society, and overall health of group A were significantly higher than those of group B, while physical score, fatigue, nausea, vomiting, and pain were lower than those of group B, which were statistically significant ( P < 0.05 ). Both groups of patients had complications after the operation, and they were asked to be followed up at the outpatient clinic 3 months after the operation. All patients recovered well. There were 19 and 18 patients in groups A and B, respectively, complaining of improvement in clinical symptoms, and the difference was not statistically significant ( P < 0.05 ). Conclusion. With the support of digital three-dimensional reconstruction and 3D printing technology, complex operations can be accurately performed, improving the efficacy and safety of patients after EC surgery, improving patient outcomes and quality of life, improving EC positioning accuracy, and reducing tumor residue.

lncRNA NBAT1 Inhibits Cell Metastasis and Promotes Apoptosis in Endometrial Cancer by Sponging miR-21-5p to Regulate PTEN

Objective. Long noncoding RNA neuroblastoma-associated transcript 1 (NBAT1) is implicated in the progression of various cancers. Nevertheless, its biological function in endometrial cancer (EC) remains unknown. Methods. The levels of NBAT1, miR-21-5p, and PTEN in EC cells and EC tissues were examined by RT-qPCR. Western blot was carried out to assess the protein expression of PTEN. The dual-luciferase reporter assay was conducted to explore the interactions among NBAT1, miR-21-5p, and PTEN. The effect of NBAT1 on EC proliferation, metastasis, and apoptosis was evaluated by CCK-8, transwell assays, wound healing, and flow cytometry. miR-21-5p mimics or NBAT1+miR-21-5p were transfected into HEC-1A and Ishikawa cells to investigate whether NBAT1 regulated EC tumorigenesis via sponging miR-21-5p. Results. NBAT1 is downregulated, and miR-21-5p is upregulated in EC cells and tumor tissues. Overexpression of NBAT1 inhibits the proliferation, migration, and invasion abilities of EC cells and facilitated apoptosis. NBAT1 directly binds and negatively regulates miR-21-5p in EC. miR-21-5p mimics reverses the effect of lncRNA NBAT1 overexpression on the proliferation and migration of EC cells. PTEN is a downstream gene of miR-21-5p. lncRNA NBTA1 elevates PTEN expression via sponging miR-21-5p. Conclusions. lncRNA NBAT1 acts as a tumor suppressor in EC via regulating PTEN through sponging miR-21-5p.

Construction of Endometrial Carcinoma ceRNA Network and Screening of Key Genes Based on TCGA Database

Objective. Long noncoding RNA (lncRNA) has received more and more attention in human tumor research. This study is aimed at clarifying the regulatory network of lncRNAs-microRNAs- (miRNAs-) mRNAs and at determining the relevant targets in the development of endometrial cancers. Methods. Download the miRNA, mRNA, and lncRNA expression profile data of endometrial cancer patients from TCGA; use the “DESeq2” package of R software to identify the differential expression of miRNAs, mRNAs, and lncRNAs; construct a network of ceRNA; and perform gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment assessment on mRNAs in the network of ceRNA; string and Cytoscape 3.7.2 perform PPI assessment on target genes and TOP 10 hub gene screening; Cytoscape 3.7.2 computer program was employed for constructing the lncRNA-miRNA-TOP10 hub mRNA network diagram to determine the signal axis; StarBase database to verify the Top10 hub mRNA expression; the “survival” package in R computer program was implemented to analyze the survival rate of all genes on the lncRNA-miRNA-Top10 hub mRNA network diagram; RT-qPCR to verify the expression level of genes on the signal axis. Results. 1119 differential mRNAs, 14 differential lncRNAs, and 65 differential miRNAs were screened in TCGA; we constructed a ceRNA regulatory network composed of 5 DELs, 7 DEMs, and 90 DEGs; String combined with Cytoscape to screen out Top10 hub genes, namely: LEFTY1, LIN28A, LHX3, ST8SIA3, CEP55, FBXO32, DCN, ANGPTL1, ADRA1A, and KCNMA1; the StarBase database verification results show that ADRA1A, ANGPTL1, FBXO32, KCNMA1, and DCN are downregulated in endometrial cancer tissues; LEFTY1, LIN28A, LHX3, ST8SIA3, and CEP55 are upregulated in endometrial cancer; the constructed lncRNA-miRNA-hub Top10 mRNA network map identified CTD-2314B22, RP11-89 K21/hsa-miR-143, hsa-miR-424/LEFTY1, LIN28A, LHX3, ST8SIA3, and CEP55 signal axis; survival analysis results show that CTD-2314B22, RP11-89 K21, hsa-miR-96, hsa-miR-211, LHX3, ST8SIA3, and DCN are all related to survival; RT-qPCR results indicate CTD-2314B22, RP11-89 K21, LEFTY1, LIN28A, LHX3, ST8SIA3, and CEP55 are upregulated in endometrial cancer cells, and hsa-miR-143 and hsa-miR-424 are downregulated in endometrial cancer cells. Conclusion. From the perspective of the lncRNA-miRNA-mRNA network, our study identified CTD-2314B22, RP11-89 K21/hsa-miR-143, hsa-miR-424/LEFTY1, LIN28A, LHX3, ST8SIA3, and CEP55 signal axis, which can present considerably potent biomarkers and therapeutic targets for treating endometrial cancer.

Controversy on Positive Peritoneal Cytology of Endometrial Carcinoma

Endometrial carcinoma (EC) is one of the most common gynecological malignancies. Its incidence rate has been increasing year by year. The prognostic factors and treatment strategies of EC have aroused wide concern. The effects of peritoneal cytology on the prognosis and treatment of EC remain controversial. Some factors, such as differentiation degree, muscle invasion, and tumor size, are related to positive peritoneal cytology. Hysteroscopy is commonly used in the diagnosis and treatment of endometrial cancer, but hysteroscopic surgery may cause the tumor to spread into the abdominal cavity, resulting in positive peritoneal cytology. In this review, we discuss the factors related to positive peritoneal cytology and the influence of positive peritoneal cytology on the prognosis of endometrial cancer. Suspicious positive peritoneal cytology may be an independent risk factor for endometrial cancer. The positive rate of peritoneal tumor cells in type II endometrial cancer is higher than other cells and is an independent risk factor for type II endometrial cancer. We also discuss the effects of peritoneal cytology on treatment decisions. Aggressive treatments seem to be more beneficial for patients with positive ascites cytology, but there is a lack of large-scale prospective clinical studies on their effectiveness and safety. The application of peritoneal cytology for endometrial cancer has been decreased in recent years. We believe that peritoneal cytology is necessary for this type of cancer. However, more studies on peritoneal cytology in endometrial cancer should be carried out.

Identification of the Ferroptosis-Associated Gene Signature to Predict the Prognostic Status of Endometrial Carcinoma Patients

Endometrial carcinoma (EC) is one of the most common gynecological carcinomas. As previously described, ferroptosis was reported to exhibit a significant association with the development of malignant neoplasms. Nevertheless, there are few studies towards the association between the implication of ferroptosis-related genes (FRGs) and the prognostic status of patients with EC. Our study demonstrated that ferroptosis-related genes were evidently differently expressed in EC. Further analysis showed that SLC7A11, SAT1, CDKN1A, and TP5MC3 expression was linked to the low stage, grade of pTNM, and longer survival time. Bioinformatics analysis demonstrated that these ferroptosis-related regulators played a crucial role in EC by modulating multiple biological processes, such as cell cycle, citrate cycle (TCA cycle), metabolism-related pathways, ERK activation, p53 signaling pathway, cellular senescence, TAp63 pathway, and Notch signaling pathway. Of note, our results showed that ATP5MC3, CDKN1A, and SLC7A11 expression was dramatically positively related with the tumor mutational burden (TMB) score in EC. However, we did not observe a significant correlation between SAT1 and the TMB score in EC. These findings for the first time demonstrated that ferroptosis was displayed crucially in EC progression. We speculated that our findings offered novel targets and strategies for personalized treatment.

Application of Single-Hole Laparoscopy and Sentinel Lymph Node Imaging in Early Endometrial Carcinoma in Special Population

Aim. To explore the clinical efficacy of single-hole laparoscopy combined with sentinel lymph node imaging in the treatment of early endometrial carcinoma in a special population. Method. A retrospective analysis was made on the clinicopathological data of 8 patients with early endometrial carcinoma who underwent extra fascial total hysterectomy plus double adnexal resection and pelvic sentinel lymphadenectomy by transumbilical single-hole laparoscopy in Jiaxing Maternal and Child Health Hospital from Apr. 2019 to Apr. 2021. Result. Single-hole laparoscopy and sentinel lymph node imaging were successfully performed in 8 patients with early endometrial carcinoma, and none of them was converted to porous or laparotomy. At the same time, all 8 patients have a high demand for body shape. All FIGO pathological grades were grade I before operation. Operation time is 160.87 ± 40.61   min , amount of bleeding is 68.75 ± 12.31   ml , the catheter was removed for 2 days, anal exhaust time is 30.13 ± 10.99   h , and postoperative hospital stay is 4.00 ± 1.07   d . There was no related organ injury during the operation, no case of blood transfusion, or case of poor wound healing. The evaluation of postoperative satisfaction was very satisfactory. Conclusion. The application of single-hole laparoscopy and sentinel lymph node imaging in the treatment of early endometrial carcinoma in the special population should be safe and feasible with high satisfaction.

Comprehensive Analysis of the Control of Cancer Stem Cell Characteristics in Endometrial Cancer by Network Analysis

Background. Cancer stem cells play an important role in endometrial cancer (EC). It is closely related to self-renewal and therapeutic resistance of EC. Methods. In this study, WGCNA (weighted gene coexpression network analysis) was used to analyze the relationship between genes and clinical features. We also performed immune cell infiltration analysis of a key module by using ImmuCellAI (Immune Cell Abundance Identifier). Then, key genes were verified in the GEO database. Finally, causal relationship analysis and protein-protein interaction analysis were performed in DisNor tool and STRING. Result. The mRNA expression-based stemness index (mRNAsi) is significantly lower in normal tissues and is significantly higher in individuals with stage IV or high-grade cancer and those who are obese or postmenopausal. Nineteen key genes (ORC6, C1orf112, RAD54L, SGO2, BUB1, PLK4, KIF18B, BUB1B, TTK, NCAPG, XRCC2, CENPF, KIF15, RACGAP1, ARHGAP11A, TPX2, KIF14, KIF4A, and NCAPH) that were enriched mainly in terms related to the cell cycle and DNA replication were selected by weighted gene coexpression network analysis (WGCNA). Based on the key modules, the numbers of NKT cells, NK cells, and neutrophils in the normal group were significantly higher than those in the cancer group. PLK1, CDK1, and MAD2L1, which were correlated with upstream genes, may be an regulated upstream of key genes. Conclusion. PLK1, CDK1, and MAD2L1 which were strongly correlated with upstream genes may be a regulated upstream of key genes.

A Computationally Virtual Histological Staining Method to Ovarian Cancer Tissue by Deep Generative Adversarial Networks

Histological analysis to tissue samples is elemental for diagnosing the risk and severity of ovarian cancer. The commonly used Hematoxylin and Eosin (H&E) staining method involves complex steps and strict requirements, which would seriously impact the research of histological analysis of the ovarian cancer. Virtual histological staining by the Generative Adversarial Network (GAN) provides a feasible way for these problems, yet it is still a challenge of using deep learning technology since the amounts of data available are quite limited for training. Based on the idea of GAN, we propose a weakly supervised learning method to generate autofluorescence images of unstained ovarian tissue sections corresponding to H&E staining sections of ovarian tissue. Using the above method, we constructed the supervision conditions for the virtual staining process, which makes the image quality synthesized in the subsequent virtual staining stage more perfect. Through the doctors’ evaluation of our results, the accuracy of ovarian cancer unstained fluorescence image generated by our method reached 93%. At the same time, we evaluated the image quality of the generated images, where the FID reached 175.969, the IS score reached 1.311, and the MS reached 0.717. Based on the image-to-image translation method, we use the data set constructed in the previous step to implement a virtual staining method that is accurate to tissue cells. The accuracy of staining through the doctor’s assessment reached 97%. At the same time, the accuracy of visual evaluation based on deep learning reached 95%.

Efficacy and Side Effects of Irinotecan Combined with Nedaplatin versus Paclitaxel Combined with Cisplatin in Neoadjuvant Chemotherapy for Locally Advanced Cervical Cancer and Tumor Marker Analysis: Based on a Retrospective Analysis

Objective. A case-control study was adopted to investigate the efficacy and side effects of irinotecan combined with nedaplatin (NP) versus paclitaxel combined with cisplatin for locally advanced cervical cancer (CC) neoadjuvant chemotherapy (NACT) and to analyze the changes in tumor marker levels. Methods. A total of 96 patients with locally advanced CC who were treated from October 2019 to October 2021 were enrolled in our hospital as the research subjects, and their clinical data were collected for retrospective analysis and grouped according to their treatment regimens. Among them, 53 patients received paclitaxel combined with cisplatin as the control group, and the other 43 patients received irinotecan combined with NP as the observation group. The clinical effectiveness of neoadjuvant chemotherapy and alterations in tumor markers (CEA, AFP, CA125, and SCCA) were compared between the two groups. The incidence of common chemotherapy side effects was observed and compared between the two groups, including nausea and vomiting, abdominal pain and diarrhea, liver function impairment, bone marrow suppression, transient hyperglycemia, rash, ECG abnormalities, peripheral neurotoxicity, and muscle aches and pains. Results. The clinical efficiency of neoadjuvant chemotherapy was 97.67% in the observation group and 81.13% in the control group, with no statistically significant difference between the groups ( P > 0.05 ). There was no significant difference in CEA, AFP, and CA125 between the two groups before and after chemotherapy, but the decrease of SCCA before and after chemotherapy was statistically significant. There was no significant difference in the incidence of liver function damage, myelosuppression, abnormal ECG, and rash between the two groups ( P > 0.05 ). There are statistically significant differences in the incidence of nausea and vomiting, transient hyperglycemia, peripheral neurotoxicity, and muscle aches between the observation and control groups ( P < 0.05 ). The incidence of nausea and vomiting, transient hyperglycemia, peripheral neurotoxicity, and muscle aches was higher in the control group than in the observation group, with statistically significant differences ( P < 0.05 ). The difference in the incidence of diarrhea and abdominal pain between the observation group and the control group was statistically significant ( P < 0.05 ), and the incidence of diarrhea and abdominal pain in the observation group was higher than that in the control group. Conclusion. Irinotecan in combination with nedaplatin can be an effective neoadjuvant chemotherapy regimen for advanced localized cervical cancer, particularly in patients with combined diabetes.

Privacy Preserved Cervical Cancer Detection Using Convolutional Neural Networks Applied to Pap Smear Images

Image processing has enabled faster and more accurate image classification. It has been of great benefit to the health industry. Manually examining medical images like MRI and X‐rays can be very time‐consuming, more prone to human error, and way more costly. One such examination is the Pap smear exam, where the cervical cells are examined in laboratory settings to distinguish healthy cervical cells from abnormal cells, thus indicating early signs of cervical cancer. In this paper, we propose a convolutional neural network‐ (CNN‐) based cervical cell classification using the publicly available SIPaKMeD dataset having five cell categories: superficial‐intermediate, parabasal, koilocytotic, metaplastic, and dyskeratotic. CNN distinguishes between healthy cervical cells, cells with precancerous abnormalities, and benign cells. Pap smear images were segmented, and a deep CNN using four convolutional layers was applied to the augmented images of cervical cells obtained from Pap smear slides. A simple yet efficient CNN is proposed that yields an accuracy of 0.9113% and can be successfully used to classify cervical cells. A simple architecture that yields a reasonably good accuracy can increase the speed of diagnosis and decrease the response time, reducing the computation cost. Future researchers can build upon this model to improve the model’s accuracy to get a faster and more accurate prediction.

FTX Regulated miR-153-3p/FOXR2 to Promote Cisplatin Resistance in Ovarian Cancer

Purpose. The present study was aimed at exploring the role of FTX in cisplatin (DDP) resistance in ovarian cancer (OC). Methods. QPCR was applied to evaluate mRNA expression in OC tissue and cells. CCK-8 assay was conducted to evaluate cell proliferation. Transwell chamber assay was performed to evaluate invasion of SKOV3/DDP cells. The protein expression was evaluated via western blot assay. Flow cytometry was performed to evaluate the apoptosis of SKOV3/DDP cells. Results. The expression of FTX in DDP-resistant cells was observably higher in contrast to DDP-sensitive cells and normal ovarian cells. FTX was higher expressed in DDP-resistant tissues by comparison with DDP-sensitive tissues. Knockdown of FTX obviously suppressed the proliferation ability invasion ability of SKOV3/DDP cells. Knockdown of FTX obviously enhanced apoptosis of SKOV3/DDP cells. miR-153-3p was proved to be directly regulated by FTX via the luciferase reporter assays. By comparison with normal cells, miR-153-3p was lower expressed in OC cells. miR-153-3p was lower expressed in SKOV3/DDP cells in contrast to SKOV3 cells. More interestingly, FTX reversed the inhibiting influence of miR-153-3p on cisplatin resistance of OC cells. Moreover, miR-153-3p was proved to directly regulate FOXR2. Knockdown of miR-153-3p attenuated the inhibitory influence of knockdown FOXR2 on cisplatin resistance of OC cells. Conclusion. FTX regulated miR-153-3p/FOXR2 to promote cisplatin resistance via inhibiting the apoptosis and promoting the viability and invasion in OC.

Period Analysis of Intraracial Differences in Incidence and Survival Rates in Epithelial Ovarian Cancer

Background. To explain the difference in the incidence and relative survival in a population-based cohort of women with epithelial ovarian cancer (EOC) postdiagnosis in the last forty years. EOC is the most common type of all ovarian cancers, but there is inadequate information about the variations related to long-term EOC survival. Methods. We acquired the incidence and relative survival rate data from the Surveillance, Epidemiology, and End Results (SEER) registries to analyze the epidemiological variations from 1974 to 2013 in EOC-affected individuals. The survival disparities in EOC-specific individuals due to age, race, and socioeconomic status (SES) were performed by Kaplan-Meier analysis. The Results. The overall incidence of EOC progressively declined to 9.0 per 100,000 from 11.4 in the last forty years. The median survival rate improved to 48 months in the first decade from a previous of 27 months in the fourth decade. The 5-year relative survival rate (RSR) increased to 44.3% that was previously 32.3% at the same time. However, between whites and blacks, an increase from 11 to 18 months was observed in the median survival differences. Between the low and high poverty groups, it was increased from 7 months to 12 months, respectively. Conclusions. The incidence rate of RSR and EOC-specific individuals in the last forty years was improved. However, the survival rates among different races and SES differed over time.

Detection of BRCA1/2 Mutation and Analysis of Clinicopathological Characteristics in 141 Cases of Ovarian Cancer

Breast cancer susceptibility genes 1 and 2 (BRCA1 and BRCA2) are known biomarkers for hereditary ovarian cancer (OC). However, a comprehensive association study between BRCA1/2 mutation spectrum and clinicopathological characteristics in Chinese ovarian cancer patients has not been performed yet to our best knowledge. To fill in this gap, we collected BRCA1/2 sequencing data and clinical information of 141 OC patients from Fujian Cancer Hospital between April 2018 and March 2020. The clinical information includes the age of onset, FIGO staging, pathological types, serum 125 detection level, lymph node metastasis, distant metastasis, the expression of Ki67, and disease history of the patient and his/her family. We then studied their associations by software SciPy 1.0. As a result, we detected pathogenic and potentially pathogenic BRCA1/2 mutations in 27 out of 141 patients (19.15%). Among the 27 patients with mutations, the major type of mutation was frameshift, which was observed in 12 patients (44.4%). Most of the mutation sites were distributed on exons 10 and 11, accounting for 48.1% (13/27) and 22.2% (6/27), respectively. In terms of histological classification, high-grade serous adenocarcinoma accounted for 79.43% of the 141 samples. The BRCA1/2 mutation group was all high-grade serous adenocarcinoma, accounting for 24.1% (27/112) of this group. The incidence of pathogenic mutation in BRCA1 and BRCA2 was 15.7% (19/112) and 7.27% (8/112), respectively. Univariate analysis showed that there was no significant difference between patients with BRCA1/2 mutation and others in age-of-onset, FIGO stage, pathological types, serum CA125 level, lymph node metastasis, the expression of Ki67, and personal and family disease history. However, there are significant differences between patients with BRCA1/2 mutation and others in distant metastasis rate ( P < 0.002 ). In addition, the BRCA1/2 mutation rate in 141 ovarian cancer patients was similar to those reported in other studies in China. Nearly one-quarter of high-grade serous carcinomas had BRCA1/2 mutations. In conclusion, our study indicated that patients with BRCA1/2 mutations were more likely to undergo distant metastasis, and BRCA1/2 mutation detection should be performed for patients with high-grade serous adenocarcinoma to guide the selection of clinical treatment options.

The Modeling Analysis and Effect of CHI3L1 and CD31-Marked Microvessel Density in the Occurrence and Development of Cervical Squamous Cell Carcinoma

Background. Chitinase-3-like protein 1 (CHI3Ll) has been identified as a novel tumor marker in several cancers. The objective of this study was to detect the expression of Chitinase-3-like protein 1 (CHI3L1) and CD31-labeled microvessel density (MVD) in cervical squamous cell carcinoma (CSCC) and to assess its prognostic impact. Methods. Elivision™ plus immunohistochemical method was used to detect CHI3L1 expression and MVD in different cervical tissues. We analyzed the relationship between CHI3L1 and MVD in CSCC tissues and investigated the relationship between CHI3L1, MVD, and clinicopathological parameters. Univariate and multivariate survival analyses were performed to assess the impact on progression-free survival (PFS) and overall survival (OS). Results. The positive expression rate of CHI3L1 protein in CSCC tissues (69.9%, 72/103) was significantly higher than that in high-grade cervical intraepithelial lesions (53.3%, 32/60), low-grade cervical intraepithelial lesions (25%, 15/60), and normal cervical tissues (16.7%, 10/60). MVD values ranged from 6 to 64 in CSCC, and no microvascular formation was observed in normal cervical tissues, high-grade intraepithelial lesions, or low-grade intraepithelial lesions. The high expression of CHI3L1 and MVD was significantly correlated with the invasion depth, differentiation degree, vascular invasion, and lymph node metastasis of CSCC (allP<0.05). In CSCC, the expression of MVD in the CHI3L1 high-expression group (41.35±9.056) was significantly higher than that in the CHI3L1 low-expression group (23.26±11.000,P<0.05). On univariate Kaplan–Meier analysis, FIGO stage, tumor diameter, lymph node metastasis, vascular invasion, CHI3L1, and MVD of CSCC were related to the prognosis of PFS and OS (allP<0.05); however, CHI3L1 and MVD were not independent prognostic factors. Conclusion. CHI3L1 may be involved in the progression of cervical cancer. Its high expression can promote neovascularization in the tumor microenvironment. CHI3L1 is a potential therapeutic target in the context of cervical cancer.

PDP1 Promotes Cell Malignant Behavior and Is Associated with Worse Clinical Features in Ovarian Cancer Patients: Evidence from Bioinformatics and In Vitro Level

PDP1 has been reported in multiple diseases. However, it has not been fully explored in ovarian cancer (OC). The public data was downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Differentially expressed gene analysis was conducted out using the limma package. Prognosis analysis was performed using the survival package. Gene Set Enrichment Analysis (GSEA) was performed using the fgsea package. Immune infiltration analysis was performed based on the CIBERSORT algorithm. CCK8 assay was used to evaluate the cell proliferation ability of cancer cells. Transwell assay was used for the invasion and migration ability. Our result showed that PDP1 was overexpressed in OC tissue in RNA and protein level based on multiple databases (TCGA, GSE18520, GSE27651, and GSE54388). At the same time, we found PDP1 was correlated with poor prognosis and worse clinical parameters. In vitro experiment showed that PDP1 could significantly promote proliferation, invasion, and migration ability of OC cells. GSEA analysis showed that in the OC patients with high PDP1 expression, the pathway of IL6/JAK/STAT3 signaling, interferon-alpha response, apoptosis, adipogenesis, KRAS signaling, and IL2/STAT5 signaling was activated, which might be responsible for its oncogenic effect in OC. Immune infiltration analysis indicated that PDP1 was positively correlated with activated myeloid dendritic cells, resting CD4 memory T cells, neutrophil, and M1 and M2 macrophages, yet negatively correlated with M0 macrophages, plasma B cells, γδT cells, and activated CD4 memory T cells. Drug sensitivity analysis showed a negative correlation between PDP1 expression and the IC50 of bleomycin and gemcitabine, yet a positive correlation of cisplatin, indicating that the OC patients with high PDP1 expression might be more sensitive to bleomycin and gemcitabine and more resistant to cisplatin. PDP1 could facilitate OC progression and is associated with patient prognosis and chemosensitivity, making it an underlying biomarker of OC.

Molecular Analysis of Prognosis and Immune Infiltration of Ovarian Cancer Based on Homeobox D Genes

Background. Homeobox D (HOXD) genes were associated with cancer pathogenesis. However, the role of HOXD genes in ovarian cancer (OC) and the possible mechanisms involved are unclear. In this study, we analyzed the function and regulatory mechanisms and functions of HOXD genes in OC based on comprehensive bioinformatics analysis. Methods. Expression of HOXD1/3/4/8/9/10/11/12/13 mRNA was analyzed between OC tissue and normal tissue using ONCOMINE, GEO, and TCGA databases. The relationship between HOXD expression and clinical stage was studied by GEPIA. The Kaplan-Meier plotter was used to analyze prognosis. cBioPortal was used to analyze the mutation and coexpression of HOXDs. GO and KEGG analyses were performed by the DAVID software to predict the function of HOXD coexpression genes. Immune infiltration analysis was used to evaluate the relationship between the expression of HOXD genes and 24 immune infiltrating cells. Results. The expression of HOXD3/4/8/9/10/11 was significantly lower in OC tissues than in normal ovarian tissues, while the expression of HOXD1/12/13 was significantly higher in OC tissues. The expression of HOXD genes was associated with FIGO stage, primary therapy outcome, tumor status, anatomic neoplasm subdivision, and age. The expression levels of HOXD1/3/4/8/9/10 correlated with tumor stage. HOXD1/8/9 could be served as ideal biomarkers to distinguish OC from normal tissue. Low HOXD9 expression was associated with shorter overall survival (OS) (HR: 0.75; 95% CI: 0.58–0.98; P = 0.034 ) and progression-free survival (PFS) (HR: 0.69; 95% CI: 0.54–0.87; P = 0.002 ). The HOXD coexpression genes were associated with pathways including cell cycle, TGF-beta signaling pathway, cellular senescence, and Hippo signaling pathway. HOXD genes were significantly associated with immune infiltration. Conclusion. The expression of HOXD genes is associated with clinical characteristics. HOXD9 is a new biomarker of prognosis in OC, and HOXD1/4/8/9/10 may be potential therapeutic targets. The members of the HOXD genes may be the response to immunotherapy for OC.

Comparison of Effectiveness as well as Advantages and Disadvantages of Different Dimensions of Hysterosalpingo-Contrast Sonography for Diagnosis of Lesions Associated with Female Infertility

Background and Objective. With social pressures and changes in lifestyle habits, the incidence of female infertility has increased in recent years. How to make timely and accurate assessment of the patency of the fallopian tubes in infertile women is of great importance in the clinical management of infertility. Therefore, this study aims to provide a reference for the future clinical application of hysterosalpingo-contrast sonography (HyCoSy) by comparing the advantages and disadvantages of different dimensions of HyCoSy for the diagnosis of female infertility. Methods. Forty subjects who underwent routine two-dimensional (2D) vaginal ultrasound, three-dimensional HyCoSy (3D-HyCoSy), and four-dimensional HyCoSy (4D-HyCoSy) examinations from January 2021 to July 2022 at the ultrasound department of Pukou Branch of Jiangsu Province Hospital were enrolled to this study. Fallopian tubal recanalization by hydrotubation (FTRH) was used as the gold standard to compare the efficacy of 2D vaginal ultrasound, 3D-HyCoSy, and 4D-HyCoSy in assessing the subjects for the presence of polyps, myomas, and other occupants in the uterine cavity or uterine adhesions. Results. A total of 18 cases of uterine cavity lesions, 11 of pelvic lesions, and 11 of ovarian lesions were identified by FTRH, while 80 fallopian tubes were found in 40 patients and 71 tubal obstructions were detected by FTRH. Vaginal ultrasound assessment of uterine cavity, pelvis, ovarian lesions, and tubal obstruction was moderately consistent with FTRH ( Kappa = 0.616 , 0.673, 0.654, and 0.640), 3D-HyCoSy was in good agreement with FTRH ( Kappa = 0.812 , 0.910, 0.906, and 0.894), and 4D-HyCoSy was in good agreement with FTRH ( Kappa = 0.914 , 0.903, 1.000, and 0.942), with 4D-HyCoSy being in good agreement with FTRH had the highest agreement. Conclusion. 4D-HyCoSy can be used as an effective tool for clinical diagnosis of female tubal obstruction infertility and provide a reference basis for the design of subsequent clinical treatment plans.

Immune Subtype Profiling and Establishment of Prognostic Immune-Related lncRNA Pairs in Human Ovarian Cancer

This study collected immune-related genes (IRGs) and used gene expression data from TCGA database to construct a molecular subtype of ovarian cancer (OV) based on immune-related lncRNA gene pairs (IRLnc_GPs). The relationships between molecular subtypes and prognosis and clinical characteristics were further explored. IRGs were acquired from the ImmPort database, and round-robin pairing of immune-related lncRNAs was performed. The NMF algorithm was used to identify molecular subtypes, and the immune score of a single sample was calculated through ESTIMATE, TIMER, ssGSEA, MCPcounter, and CIBERSORT. The relationship between molecular subtypes and immune microenvironments was identified. A hypergeometric test was used to test the lncRNA pairs among the OV molecular subtypes (C1 and C2 subtypes). The BH method was used to screen the different lncRNA pairs, and a predictive risk model was constructed and verified. Finally, correlation analysis between the risk model, immune checkpoint genes, and chemotherapy drugs was carried out. Based on IRLnc_GP to classify 373 OV samples of TCGA, the samples were divided into two subtypes, and the prognosis between the subtypes showed significant differences. The C1 subtype with a poor prognosis was more related to the pathways of tumor occurrence and development. We identified 180 differential lncRNA pairs between subtypes and constructed a prognostic risk model based on 8 IRLnc_GPs. In the independent dataset, the distribution of subtypes in functional modules was different and highly repeatable. There were significant differences in the molecular and clinical characteristics of the subtypes and the drug sensitivity of immunotherapy/chemotherapy. In conclusion, the risk model established based on IRLnc_GP can better evaluate the prognosis of OV samples and can also assess the effects of different drug treatments in the high- and low-risk groups, providing new insights and ideas for the treatment of OV.

Potential Diagnostic and Prognostic Values of CBX8 Expression in Liver Hepatocellular Carcinoma, Kidney Renal Clear Cell Carcinoma, and Ovarian Cancer: A Study Based on TCGA Data Mining

Background. Chromobox protein homolog 8 (CBX8), a transcriptional repressor, participates in many biological processes in various carcinomas. Cell differentiation, aging, and cell cycle progression are examples of such processes. It is critical to investigate CBX8 expression and its relationship with clinicopathological characteristics in liver hepatocellular carcinoma (LIHC), kidney renal clear cell carcinoma (KIRC), and ovarian cancer (OV) to investigate CBX8’s potential diagnostic and prognostic values. Methods. TCGA and CPTAC databases were used to compare the data between cancer and matched normal tissues on RNA and protein expression profiles and their relevant clinical information to determine the relationship between CBX8 and clinicopathological features. Kaplan–Meier analyses were used to assess CBX8 relationship’s with disease-free survival (DFS), relapse-free survival (RFS), and overall survival (OS). The multivariate Cox regression analysis was used to identify independent risk factors which affect prognosis. DNA methylation and genetic changes and their impact on prognoses were evaluated by cBioPortal and MethSurv websites. Spearman’s correlation was used to determine the relationship of CBX8 expression with somatic mutation. Tumor immune estimation resource (TIMER) was adopted to investigate the relationship between CBX8 and immune cell infiltration (ICI). CBX8-relevant genes and proteins are analyzed by EnhancedVolcano and STRING databases. The gene set enrichment analysis (GSEA) was performed to investigate the potential functions of CBX8. Results. CBX8 RNA and protein overexpression were confirmed in LIHC, KIRC, and OV ( p < 0.05 ). High CBX8 was significantly related to the clinical features and poor prognoses. The CBX8 genetic alteration rate was 3%. DNA methylation was also associated with prognoses. CBX8 closely interacted with ICI, TMB, MSI, purity, and ploidy. GO analyses revealed that CBX8-associated genes were enriched in biological processes, cell cycle regulation, and molecular functions. KEGG analyses exhibited that CBX8 was gathered in signaling pathway regulation. GSEA revealed that cell cycle, DNA replication, and Wnt signaling pathways were differentially enriched in the high CBX8 expression group. Conclusions. CBX8 could be a potential diagnostic and prognostic biomarker for LIHC, KIRC, and OV cancers.

Effect of PARP Inhibitor Combined with Bevacizumab on Platinum-Resistant Recurrent Ovarian Epithelial Carcinoma

Objective. This study was aimed at investigating the efficacy of PARP inhibitor combined with bevacizumab in the treatment of platinum-resistant recurrent ovarian epithelial carcinoma. Methods. A total of 84 patients with platinum-resistant recurrent ovarian epithelial carcinoma treated in our hospital from May 2017 to June 2018 were selected as the research objects. The patients were divided into observation group ( n = 42 ) and control group ( n = 42 ) according to random number table method. The observation group was treated with olaparib combined with bevacizumab, while the control group was treated with albumin-bound paclitaxel combined with bevacizumab, and the clinical efficacy of the two groups was observed. The levels of serum carbohydrate antigen 125 (CA125), carbohydrate antigen 199 (CA199), and epididymal protein 4 (HE4) were determined. The levels of miRNA124, mirNA-21, and miRNA-203 in the two groups were detected. The incidence of adverse reactions was compared between the two groups. The quality of life of the two groups was assessed using FACT-G scale. The drug safety of the two groups was observed. All patients were followed up for 3 years, and the survival time of the two groups was recorded. The Kaplan-Meier method was used to analyze the survival of the two groups. Results. The overall response rate (ORR) (69.05%) and disease control rate (DCR) (88.10%) of the observation group were higher than those of the control group (40.48% and 66.67%), and the differences were statistically significant (both P < 0.05 ). After treatment, the levels of serum CA125, CA199, HE4, miRNA124, miRNA-21, and miRNA-203 and the improvement degree of quality of life score in the observation group were greater than those in the control group, with statistical significances (all P < 0.05 ).The 1-year, 2-year, and 3-year survival rates of the observation group (97.62%, 88.10%, and 80.95%) were higher than those of the control group (71.43%, 57.14%, and 47.62%), with statistical significances (all P > 0.05 ). Conclusion. PARP inhibitor combined with bevacizumab had good effect in the treatment of platinum-resistant recurrent ovarian epithelial carcinoma and can effectively improve the survival time and quality of life of patients.

A Clinical Diagnostic Value Analysis of Serum CA125, CA199, and HE4 in Women with Early Ovarian Cancer: Systematic Review and Meta-Analysis

Objective. To evaluate the value of combined detection of serum CA125, CA199, and HE4 in the diagnosis of ovarian cancer. Methods. Relevant articles retrieved from PubMed, Elsevier Science, Springer, China National Knowledge Infrastructure (CNKI), Wanfang, and VIP databases were screened strictly according to inclusion and exclusion criteria. Included literature published from January 2005 to December 2021. (2) Serum HE4, CA125, CA199, and their combination for ovarian cancer diagnostic tests were studied, and healthy subjects or patients with the benign disease were taken as a control group. (3) Pathological tissue diagnosis as the gold standard. (4) Complete original data can be obtained. (5) The sample size was ≥20. (6) Language is limited to Chinese and English. Data features and QUADAS table were extracted from the included literature, and QUADAS evaluation tool detail table was used for the included study. Conduct quality evaluation. Statistical analysis was carried out using meta-disc software version 1.4. Appropriate effect model was selected to merge the effect size, and the forest maps of merge sensitivity, merge specificity, and merge likelihood ratio were obtained. Results. The results of meta-analysis showed that there was a statistical difference in diagnostic specificity analysis of CA125 ( OR = 1.91 , 95% CI (1.58, 2.32), P < 0.00001 , I 2 = 67 % , Z = 6.58 ); diagnostic sensitivity analysis of CA125 ( OR = 2.50 , 95% CI (1.73, 3.62), P < 0.00001 , I 2 = 0 % , Z = 4.90 ); diagnostic specificity analysis of CA199 ( OR = 1.98 , 95% CI (1.60, 2.44), P < 0.00001 , I 2 = 89 % , Z = 6.35 ); diagnostic sensitivity analysis of CA199 ( OR = 1.92 , 95% CI (1.46, 2.52), P < 0.00001 , I 2 = 73 % , Z = 4.70 ); diagnostic specificity analysis of HE4 ( OR = 2.08 , 95% CI (1.65, 2.63), P < 0.00001 , I 2 = 73 % , Z = 6.19 ); diagnostic sensitivity analysis of HE4 ( OR = 2.37 , 95% CI (1.87, 3.00), P < 0.00001 , I 2 = 83 % , Z = 7.19 ). Conclusion. In the clinical assisted diagnosis of ovarian cancer, combined detection of CA125, CA199, and HE4 has the stronger discriminant ability and higher accuracy than single detection of CA125, which can improve the diagnostic efficiency.

Establishment and Verification of Logistic Regression Model for Qualitative Diagnosis of Ovarian Cancer Based on MRI and Ultrasound Signs

Objective. To explore the establishment and verification of logistic regression model for qualitative diagnosis of ovarian cancer based on MRI and ultrasonic signs. Method. 207 patients with ovarian tumors in our hospital from April 2018 to April 2021 were selected, of which 138 were used as the training group for model creation and 69 as the validation group for model evaluation. The differences of MRI and ultrasound signs in patients with ovarian cancer and benign ovarian tumor in the training group were analyzed. The risk factors were screened by multifactor unconditional logistic regression analysis, and the regression equation was established. The self-verification was carried out by subject working characteristics (ROC), and the external verification was carried out by K-fold cross verification. Result. There was no significant difference in age, body mass index, menstruation, dysmenorrhea, times of pregnancy, cumulative menstrual years, and marital status between the two groups ( P > 0.05 ). After logistic regression analysis, the diagnostic model of ovarian cancer was established: logit   P = − 1.153 + MRI   signs : morphology × 1.459 + boundary × 1.549 + reinforcement × 1.492 + tumor   components × 1.553 + ultrasonic   signs : morphology × 1.594 + mainly   real × 1.417 + separated   form × 1.294 + large   nipple × 1.271 + blood   supply × 1.364 ; self-verification: AUC of the model is 0.883, diagnostic sensitivity is 93.94%, and specificity is 80.95%; K-fold cross validation: the training accuracy was 0.904 ± 0.009 and the prediction accuracy was 0.881 ± 0.049 . Conclusion. Irregular shape, unclear boundary, obvious enhancement in MRI signs, cystic or solid tumor components and irregular shape, solid-dominated shape, thick septate shape, large nipple, and abundant blood supply in ultrasound signs are independent risk factors for ovarian cancer. After verification, the diagnostic model has good accuracy and stability, which provides basis for clinical decision-making.

Integrated Bioinformatics Analysis for Identification of the Hub Genes Linked with Prognosis of Ovarian Cancer Patients

Background. One of the most usual gynecological state of tumor is ovarian cancer and is a major reason of gynecological tumor-related global mortality rate. There have been multiple risk elements related to ovarian cancer like the background of past cases associated with breast cancer or ovarian cancer, or excessive body weight issues, case history of smoking, and untimely menstruation or menopause. Because of unclear expressions, more than 70% of the ovarian cancer patient cases are determined during the early stage. Material and Methods. GSE38666, GSE40595, and GSE66957 were the three microarray datasets which were analyzed using GEO2R for screening the differentially expressed genes. GO, Kyoto Encyclopedia of Genes, and protein expression studies were performed for analysis of hub genes. Then, survival analysis was performed for all the hub genes. Results. From the dataset, a total of 199 differentially expressed genes (DEGs) were identified. Through the KEGG pathway study, it was noted that the DEGs are mainly linked with the AGE-RAGE signaling pathway, central carbon metabolism, and human papillomavirus infection. The survival analysis showed 4 highly expressed hub genes COL4A1, SDC1, CDKN2A, and TOP2A which correlated with overall survival in ovarian cancer patients. Moreover, the expression of the 4 hub genes was validated by the GEPIA database and the Human Protein Atlas. Conclusion. The results have shown that all 4 hub genes were found to be upregulated in ovarian cancer tissues which predict poor prognosis in patients with ovarian cancer.

Ultrasonic Elastography Combined with Human Papilloma Virus Detection Based on Intelligent Denoising Algorithm in Diagnosis of Cervical Intraepithelial Neoplasia

The aim of this research was to study the application of ultrasonic elastography combined with human papilloma virus (HPV) detection based on bilateral filter intelligent denoising algorithm in the diagnosis of cervical intraepithelial neoplasia (CIN) and provide a theoretical basis for clinical diagnosis and treatment of CIN. In this study, 100 patients with cervical lesions were selected as research objects and randomly divided into control group and experimental group, with 50 cases in each group. Patients in control group and experimental group were diagnosed by ultrasonic elastography combined with HPV detection. The experimental group used the optimized image map of bilateral filter intelligent denoising algorithm for denoising and optimization, while the control group did not use optimization, and the differences between them were analyzed and compared. The diagnostic effects of the two groups were compared. As a result, the three accuracy rates of the experimental group were 95%, 95%, and 98%, respectively; the three sensitivity rates were 96%, 92%, and 94%, respectively; and the three specificity rates were 99%, 97%, and 98%, respectively. In the control group, the three accuracy rates were 84%, 86%, and 84%, respectively; the three sensitivity rates were 88%, 84%, and 86%, respectively; and the three specificity rates were 81%, 83%, and 88%, respectively. The accuracy, sensitivity, and specificity of experiment group were significantly higher than those of control group, and the difference was statistically significant ( P < 0.05 ). In summary, the bilateral filter intelligent denoising algorithm has a good denoising effect on the ultrasonic elastography. The ultrasonic image processed by the algorithm combined with HPV detection has a better diagnosis of CIN.

Research on Radiosensitivity of the Protein Kinase B Signaling Pathway in Cervical Cancer

The main characteristics of cervical cancer are abnormal and uncontrolled cell proliferation, and it regulates cell growth, differentiation, and cell death through genetic and epigenetic changes. This paper mainly discusses the radiosensitivity of the cervical cancer protein kinase B signaling pathway and discusses the specific mechanisms that affect the occurrence and development of cervical cancer. In addition, this paper studies the effect of transient transfection knocking down the expression of TRIP4 in cervical cancer cells on the expression of key proteins in related signaling pathways and explores the mechanism of its specific effects and finds the mechanism of TRIP4’s effect on cervical cancer radiosensitivity. The findings of this study show for the first time that knocking down TRIP4 inhibits cell viability by inhibiting the P13K/AKT and MAPK/ERK pathways, and this corresponds to the first part of the experimental results, which show that knocking down TRIP4 inhibits colony formation and increases apoptosis in HeLa and SiHa cells. Moreover, simultaneous inhibition of TRIP4 and hTERT proteins can increase the radiosensitivity of cervical cancer cells. These findings indicate that the inhibition of TRIP4 may be a new type of treatment that selectively targets the P13K/AKT and MAPK/ERK pathways and hTERT pathways in cervical cancer cells and provides a therapeutic option for the treatment of cervical cancer.

Bioinformatics Analysis Reveals MCM3 as an Important Prognostic Marker in Cervical Cancer

The minichromosome maintenance complex 3 (MCM3) is essential for the regulation of DNA replication and cell cycle progression. However, the expression and prognostic values of MCM3 in cervical cancer (CC) have not been well-studied. Herein, we investigated the expression patterns and survival data of MCM3 in cervical cancer patients from the ONCOMINE, GEPIA, Human Protein Atlas, UALCAN, Kaplan-Meier Plotter, and LinkedOmics databases. The expression level of MCM3 is negatively correlated with advanced tumor stage and metastatic status. Specifically, MCM3 is significantly differentially expressed between patients in stage 1 and stage 3 cervical cancer with p value 0.0138. Similarly, the p values between stage 1 and stage 4 cervical cancer, between stage 2 and stage 3, and between stage 2 and stage 4 are 0.00089, 0.0244, and 0.00197, respectively. Not only that, cervical cancer patients with high mRNA expression of MCM3 may indicate longer overall survival but indicate shorter relapse-free survival. PRIM2 and MCM6 are positively correlated genes of MCM3. Bioinformatics analysis revealed that MCM3 might be considered a biological indicator for prognostic evaluation of cervical cancer. However, it is currently limited to bioinformatics analysis, and more clinical tissue specimens and cell experiments are needed to further explore the role of MCM3 in the occurrence and progression of cervical cancer.

Hybrid Model for Detection of Cervical Cancer Using Causal Analysis and Machine Learning Techniques

Cervical cancer has become the third most common form of cancer in the in-universe, after the widespread breast cancer. Human papillomavirus risk of infection is linked to the majority of cancer cases. Preventive care, the most expensive way of fighting cancer, can protect about 37% of cancer cases. The Pap smear examination is a standard screening procedure for the initial screening of cervical cancer. However, this manual test procedure generates many false-positive outcomes due to individual errors. Various researchers have extensively investigated machine learning (ML) methods for classifying cervical Pap cells to enhance manual testing. The random forest method is the most popular method for anticipating features from a high-dimensional cancer image dataset. However, the random forest method can get too slow and inefficient for real-time forecasts when too many decision trees are used. This research proposed an efficient feature selection and prediction model for cervical cancer datasets using Boruta analysis and SVM method to deal with this challenge. A Boruta analysis method is used. It is improved from of random forest method and mainly discovers feature subsets from the data source that are significant to assigned classification activity. The proposed model’s primary aim is to determine the importance of cervical cancer screening factors for classifying high-risk patients depending on the findings. This research work analyses cervical cancer and various risk factors to help detect cervical cancer. The proposed model Boruta with SVM and various popular ML models are implemented using Python and various performance measuring parameters, i.e., accuracy, precision, F 1 – Score , and recall. However, the proposed Boruta analysis with SVM performs outstanding over existing methods.

Development of a Novel Deep Learning-Based Prediction Model for the Prognosis of Operable Cervical Cancer

Background. Cervical cancer ranks as the 4th most common female cancer worldwide. Early stage cervical cancer patients can be treated with operation, but clinical staging system is not a good predictor of patients’ survival. We aimed to develop a novel prognostic model to predict the prognosis for operable cervical cancer patients with better accuracy than clinical staging system. Methods. A total of 13,952 operable cervical cancer patients were retrospectively enrolled in this study. The whole dataset was randomly split into a training set ( n = 9,068 , 65%), validation set ( n = 2,442 , 17.5%), and testing set ( n = 2,442 , 17.5%). Cox proportional hazard (CPH) model and random survival forest (RSF) model were used as baseline models for the prediction of overall survival (OS). Then, a deep survival learning model (DSLM) was developed for OS prediction. Finally, a novel prognostic model was explored based on this DSLM. Results. The C-indexes for the CPH and RSF model were 0.731 and 0.753, respectively. DSLM, which had four layers that had 50 neurons in each layer, achieved a C-index of 0.782 in the validation set and a C-index of 0.758 in the testing set. The novel prognostic model based on DSLM showed better performances than the conventional clinical staging system (area under receiver operating curves were 0.826 and 0.689, respectively). Personalized survival curves for individual patient using this novel model also showed notably different survival slopes. Conclusions. Our study developed a novel, practical, personalized prognostic model for operable cervical cancer patients. This novel prognostic model may have the potential to provide a more prognostic information to oncologists.

Expression of GMFB in High-Grade Cervical Intraepithelial Neoplasia and Its Role in Cervical Cancer

Cervical intraepithelial neoplasia (CIN) is a collective term for specific precancerous lesions associated with cervical cancer (CC). Although it has been affirmed with slow development of several levels of cellular changes, the existing poor prognosis calls for an urgent need to diagnose CIN at early stage and be aware of markers related to its pathogenesis and prognosis. We explored the expression level of a newly marker GMFB and its regulatory effect on CIN and CC. Patient samples and cell models were included. Bioinformatic studies were taken to predict its binding to miR-143-3p, miR-26b-5p, miR-191-5p, and miR-223-3p. Luciferase reporter and RNA pull-down assays were used to validate the prediction. Edu assay and flow cytometry were used to measure the regulation of GMFB on proliferation and apoptosis of CC cells. qRT-PCR was used for mRNA expression level detection. The results showed that GMFB was targeted by miR-143-3p, miR-26b-5p, miR-191-5p, and miR-223-3p. It had elevated expression in both CIN and CC samples. GMFB had highly prognostic value for CIN, and lymph node metastasis of CC was much associated with high GMFB expression level. Besides, silencing of GMFB inhibited CC cell proliferation and elevated cell apoptosis. In conclusion, we determined that GMFB has regulatory effect on high grade CIN and CC, which could lighten a novel way in exploring their pathogenesis and improving accuracy of prognosis.

High DHCR7 Expression Predicts Poor Prognosis for Cervical Cancer

DHCR7 is a rate-limiting enzyme in cholesterol synthesis. The expression pattern and prognostic value of DHCR7 in cervical cancer are unknown. We investigated the relationship between DHCR7 expression and clinicopathological features of cervical cancer patients. The dataset was acquired from TCGA database. The Wilcoxon rank sum test was used to explore DHCR7 expression level in cervical cancer. The Kruskal-Wallis test and the logistic regression were performed to estimate the association between the DHCR7 and clinical features. The Kaplan-Meier and Cox regression analyses were used to evaluate factors that affect cervical cancer prognosis. GSEA was used to screen the DHCR7-related pathways. We found that DHCR7 was increased in cervical cancer samples and increased DHCR7 was correlated with advanced T stage, lymph node invasion, and clinical stage ( P < 0.05 ). Patients with elevated DHCR7 levels had poorer overall survival ( P = 0.021 ), progression-free interval ( P = 0.002 ), and disease-specific survival ( P = 0.005 ). Cox analysis revealed that DHCR7 was an independent prognostic factor in cervical cancer ( P = 0.005 ). WNT activated receptor activity, G2/M checkpoint, mTORC1 signaling, KRAS signaling, regulation of cholesterol biosynthetic, FGF signaling, T-cell receptor signaling, JAK/STAT signaling cascade T cell activation, and macrophage migration were enriched in high DHCR7 phenotype. Our data also showed that DHCR7 moderately correlates with T-cell infiltration, including CD8+ T-cells. Conclusion. Increased DHCR7 expression is associated with poor survival in cervical cancer.

MRI Using Artificial Intelligence Algorithm to Evaluate Concurrent Chemoradiotherapy for Local Recurrence and Distant Metastasis of Cervical Squamous Cell Carcinoma

The aim of this study was to investigate the magnetic resonance imaging (MRI) features of patients with local recurrence and distant metastasis of cervical squamous cell carcinoma before and after concurrent chemoradiotherapy based on artificial intelligence algorithm. In this study, 100 patients with cervical squamous cell carcinoma with local recurrence and distant metastasis who underwent concurrent chemoradiotherapy were collected as the research subjects, and all underwent MRI multisequence imaging scans. At the same time, according to the evaluation criteria of solid tumor efficacy, patients with complete remission were classified into the effective group, and patients with partial remission, progressive disease, and stable disease were classified into the ineffective group. In addition, an image segmentation algorithm based on Balloon Snake model was proposed for MRI image processing, and simulation experiments were carried out. The results showed that the Dice coefficient of the proposed model segmentation of the reconstructed image was significantly higher than that of the level set model and the greedy algorithm, while the running time was the opposite ( P < 0.05 ). The lesion volume ( 38.76 ± 5.34  cm3) in the effective group after treatment was significantly smaller than that in the noneffective group ( 46.33 ± 4.64  cm3), and the rate of lesion volume shrinkage (28.71%) was significantly larger than that in the noneffective group (12.49%) ( P < 0.05 ). The relative apparent diffusion coefficient (rADC) value and rADC value change rate of the lesion after treatment in the effective group were significantly greater than those in the noneffective group ( P < 0.05 ). In summary, the image segmentation and reconstruction algorithm based on Balloon Snake model can not only improve the quality of MRI images but also shorten the processing time and improve the diagnostic efficiency. The volume regression rate and rADC value change rate of cervical squamous cell carcinoma lesion can reflect the early efficacy of concurrent chemoradiotherapy for cervical squamous cell carcinoma and have predictive value.

Effect of Comprehensive Care Based on Appropriate Chinese Medicine Techniques on Urinary Retention and Bladder Function Recovery after Total Hysterectomy in Patients with Cervical Cancer

Objective. To investigate the effect of comprehensive care based on appropriate Chinese medicine techniques on urinary retention and bladder function recovery after total hysterectomy in patients with cervical cancer. Methods. A total of 148 cases admitted after radical hysterectomy for cervical cancer from January 2019 to early September 2019 were used as the observation sample and were divided into control and experimental groups based on a randomized double-blind method. There were 74 cases each. The control group was given comprehensive care, and the experimental group was given comprehensive care based on appropriate Chinese medicine techniques. The intervention period was 2 weeks after surgery. The recovery rate of bladder function and the occurrence of urinary retention were compared between the two groups, and the duration of postoperative retention of urinary catheter, the amount of residual urine, and the feeling of urination were counted. Results. The experimental group had better urinary catheter retention time, time to first spontaneous voiding, time to get out of bed, and time to anal discharge than the control group; the experimental group had a higher rate of good bladder function recovery than the control group and better bladder recovery time, residual urine volume, and incidence of urinary retention than the control group; the patients in the experimental group had better UDI-6 scores. Conclusion. The implementation of comprehensive care based on appropriate Chinese medicine techniques can relieve patients’ difficulty in urination and improve their quality of life.

Body Weight Is a Valid Predictor of the Long-Term Prognosis of Cervical Cancer

Objective. To identify and validate effective clinical predictors for the long-term prognosis of patients with cervical cancer. Methods. Cervical cancer patients were retrieved from the TCGA database, and patients’ clinical data were collected and analyzed for the predictive value of long-term prognosis. In the other branch of the study, patients with cervical cancer and admitted to our hospital between January 1, 2016, and December 31, 2016, were retrieved and followed up for prognosis analysis. Results. In the database patient cohort of our study, 607 cases with cervical cancer were analyzed. Aneuploidy score ( p = 0.012 ), Buffa hypoxia score ( p = 0.013 ), histologic grade ( p = 0.01 ), fraction genome altered >0.4 ( p < 0.001 ), weight > 60 kg ( p < 0.001 ), height > 160 cm ( p = 0.047 ), BMI <18.5 ( p = 0.023 ), Winter hypoxia score ( p = 0.002 ), and adjuvant postoperative radiotherapy were good predictors for disease-free survival (DFS), while aneuploidy score ( p = 0.001 ), MSI sensor score > 0.5 ( p = 0.035 ), person neoplasm status ( p < 0.001 ), race ( p = 0.006 ), Ragnum hypoxia score ( p = 0.012 ), weight ( p < 0.001 ), height ( p < 0.001 ), and BMI < 18.5 ( p = 0.04 ) were good predictors for overall survival (OS). In the admitted patient cohort, age over 60 years old at the time of diagnosis was the only clinical factor influencing the long-term DFS ( p = 0.004 ). TNM stage above III ( p = 0.004 ), body weight > 70 kg ( p < 0.001 ), and complicated with other cancer ( p < 0.001 ) were clinical factor influencing the long-term OS. Conclusions. Clinical factors, especially common to both cohorts, could be used to show the long-term prognosis of cervical cancer.

Analysis of the Role and Mechanism of ZEB1 in Regulating Cervical Carcinoma Progression via Modulating PD-1/PD-L1 Checkpoint

Background. Cervical carcinoma (CC) is a common and highly malignant tumor in women. The involvement of zinc finger E-box binding homeobox 1 (ZEB1) in many kinds of tumors has been well-documented; however, its role and mechanism in CC remain to be clarified. Objective. This study investigated the mechanism of ZEB1 in modulating the growth and metastasis of CC cells. Methods. The expression of ZEB1 in CC tissues and adjacent normal counterparts was determined by reverse transcription-polymerase chain reaction (RT-PCR). The correlation between ZEB1 and patient clinicopathological indexes was analyzed. In vitro, gain and loss functions of ZEB1 were performed in C-33A and HeLa cell lines. The proliferation, migration, and invasion of CC cells were detected by Cell Counting Kit-8 (CCK-8) assay and transwell assay, respectively. The expression levels of apoptosis-related proteins such as BCL2-associated X (Bax), B-cell lymphoma-2 (Bcl2), and Caspase-3, as well as epithelial-mesenchymal transition (EMT)-associated proteins including E-cadherin, Vimentin, and Snail, were measured by Western blotting. In addition, the targeting relationship between ZEB1 and programmed death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) was predicted by bioinformatics and further verified by dual-luciferase reporter assay. Results. ZEB1 was significantly up-regulated in CC tissues compared with normal counterparts. ZEB1 overexpression promoted the migration, proliferation, and invasion of CC cells and inhibited apoptosis, while knocking down ZEB1 contributed to the opposite effects. In addition, experiments on related mechanisms confirmed that ZEB1 targeted the 3’EUTR terminal of PD-1/PD-L1 and negatively regulated its expression. And an interaction between ZEB1 and PD-1/PD-L1 was identified. Conclusion. ZEB1 can promote the proliferation and metastasis of CC cells via modulating the PD-1/PD-L1 checkpoint.

The Effect of Pilates Exercise Nursing Combined with Communication Standard-Reaching Theory Nursing and Pelvic Floor Muscle Training on Bladder Function and Family Function of Patients after Cervical Cancer Surgery

Objective. To explore the effect of Pilates exercise nursing combined with nursing based on the theory of communication compliance and pelvic floor muscle training on bladder function and family function of patients after cervical cancer surgery. Methods. The medical records of 96 postoperative cervical cancer patients treated in our hospital from November 2019 to May 2021 were selected as retrospective research objects and were divided into observation group and control group with 48 cases each according to the digital table method. The control group received nursing care based on the theory of communication compliance and pelvic floor muscle training, and the observation group received Pilates exercise therapy nursing on the basis of the control group. The differences in urinary retention, family intimacy and adaptability, bladder function, and family function evaluation scores were compared between the two groups. Results. After nursing, the residual urine volume, urination time, and urination interval of the observation group were lower than those of the control group, while the self-resolving urination rate and urination volume of the observation group were higher than those of the control group, which was statistically significant ( P < 0.05 ). Before nursing, the family intimacy and adaptability scores of the two groups of patients were not statistically significant ( P > 0.05 ). After nursing, the family intimacy score, family adaptability score, and sexual function score of the observation group were significantly higher than the control group; the comparison was statistically significant ( P < 0.05 ). After nursing, the bladder function recovery of the observation group was significantly better than that of the control group, which was statistically significant ( P < 0.05 ). Before nursing, the comparison of family function evaluation between the two groups of patients was not statistically significant ( P > 0.05 ). After nursing, the observation group’s problem solving, communication, role, emotional response, emotional intervention, behavior control, and total functional scores were lower than those of the control group, which were statistically significant ( P < 0.05 ). Conclusion. Carrying out nursing care based on the theory of communication compliance with Pilates exercise therapy for patients after cervical cancer surgery has a good nursing effect improves the patient’s family intimacy and adaptability and patient’s urinary retention and bladder function. Moreover, Pilates exercise nursing is a postoperative treatment for cervical cancer which provides a certain reference for clinical care of patients.

Identification and Validation of Invasion-Related Molecular Subtypes and Prognostic Features for Cervical Cancer

Background. As one of the main causes leading to female cancer deaths, cervical cancer shows malignant features of local infiltration and invasion into adjacent organs and tissues. This study was designed to categorize novel molecular subtypes according to cervical cancer invasion and screen reliable prognostic markers. Methods. Invasion-related gene sets and expression profiles of invasion-related genes were collected from the CancerSEA database and The Cancer Genome Atlas (TCGA), respectively. Samples were clustered by nonnegative matrix factorization (NMF) to obtain different molecular subgroups, immune microenvironment characteristics of which were further systematically compared. Limma was employed to screen differentially expressed gene sets in different subtypes, followed by Lasso analysis for dimension reduction. Multivariate and univariate Cox regression analysis was performed to determine prognostic characteristics. The Kaplan-Meier test showed the prognostic differences of patients with different risks. Additionally, receiver operating characteristic (ROC) curves were applied to validate the prognostic model performance. A nomogram model was developed using clinical and prognostic characteristics of cervical cancer, and its prediction accuracy was reflected by calibration curve. Results. This study filtered 19 invasion-related genes with prognosis significance in cervical cancer and 2 molecular subtypes (C1, C2). Specifically, the C1 subtype had an unfavorable prognosis, which was associated with the activation of the TGF-beta signaling pathway, focal adhesion, and PI3K-Akt signaling pathway. 875 differentially expressed genes were screened, and 8 key genes were finally retained by the dimension reduction analysis. An 8-gene signature was established as an independent factor predictive of the prognosis of cervical cancer. The signature performance was even stronger when combined with N stage. Conclusion. Based on invasion-related genes, the present study categorized two cervical cancer subtypes with distinct TME characteristics and established an 8-gene marker that can accurately and independently predict the prognosis of cervical cancer.

Publisher

Wiley

ISSN

1748-6718