Current Medical Science

TM4SF1 as a Prognostic Biomarker and Therapeutic Target in Cervical Cancer

Accumulating evidence suggests that transmembrane 4 L6 family member 1 (TM4SF1) is associated with the development of various cancers; yet comprehensive studies on TM4SF1 in cervical cancer are lacking. Therefore, we aimed to evaluate the prognostic value of TM4SF1 in cervical cancer, elucidate its potential oncogenic functions in this disease, and further explore its feasibility as a therapeutic target. The expression profiles and clinical information of cervical cancer patients were obtained from The Cancer Genome Atlas (TCGA) database. The expression levels of TM4SF1 were compared between cervical cancer and normal cervical tissues using the Wilcoxon rank-sum test. Kaplan-Meier analysis was employed to assess the prognostic value of TM4SF1. Furthermore, functional enrichment analyses were performed to explore the associated signaling pathways and biological functions. The methylation status of TM4SF1 was analyzed using the UALCAN and MethSurv databases. In addition, in vitro experiments were conducted to preliminarily validate the role and mechanisms of TM4SF1 in cervical cancer. TM4SF1 was overexpressed in nearly all tumors, and its overexpression was associated with poor prognosis in cervical cancer. Moreover, the correlation between TM4SF1 expression and the expression of immune cell infiltration markers and immune checkpoint genes suggested that it had potential applications in cancer immunotherapy. Western blot analysis and immunohistochemistry revealed significantly elevated protein levels of TM4SF1 in cervical cancer tissues and cells. Further studies revealed that the knockdown of TM4SF1 significantly inhibited the migration, invasion, and epithelial-mesenchymal transition (EMT) of HeLa and SiHa cells, as well as promoted their apoptosis. TM4SF1 may serve as a potential prognostic biomarker and therapeutic target for cervical cancer.

Genotype Identification of Complete Hydatidiform Moles without a Maternal Component: Attempts at a Novel 26-plex STR System

Current autosomal short tandem repeat (STR) assays can analyze the zygotic composition by comparing the allelic genes at each locus of complete hydatidiform moles (CHM), with a maternal genotype serving as an essential reference for comparative analysis. However, their application in pathology represents a challenge because of deficiency or contamination of maternal-origin tissues. This study aimed to develop a novel STR genotyping method for identifying CHM genotypes without a maternal component. Samples with the pathologic description of molar pregnancy were collected. Routine hematoxylin-eosin (HE) staining and p57 immunohistochemistry staining were conducted in accordance with standard guidelines. A novel 26-plex system was explored to classify CHM and diploid pregnancies. The system combined 22 STRs on chromosomes 21/18/13/X, 3 sex loci, and 1 quality control marker (TAF9L), enabling molecular diagnosis in the absence of maternal tissue. At last, traditional DNA typing based on villi and decidua (maternal component) of each case was used for result consistency analysis. CHM and nonmolar abortus could not be distinguished by the basic HE staining with no fetal evidence or other prominent features. DNA typing was successfully processed for all cases according to the novel 26-plex and traditional system. CHM (46XX) diagnosis required single A-STR/X-STR peaks and absent Y-chromosome markers, excluding chromosomal abnormalities via TAF9L analysis. When the villous tissue analysis revealed single peaks at X-STR/SRY loci, a 1:1 amelogenin ratio, and a 2:1 TAF9L peak ratio, these results overlapped with those of 46XY hydropic abortus or CHM. Notably, p57 immunohistochemical staining resolved the ambiguity. Consistency with traditional DNA genotyping confirmed system accuracy. This multiplex assay enhanced reliability in mole diagnosis, supporting clinical differentiation and genetic counseling. This study presents a rapid and cost-effective assay for the genotypic identification of CHM without the need for a maternal component. The method combined the characteristics of STR loci distributed across different chromosomes and developed the clinic application of forensic biomarkers.

Genome-integrated Human Papilloma Viruses Testing: A Complement to Colposcopy-guided Biopsy for Cervical Cancer Screening

Our research aims to evaluate the diagnostic accuracy of colposcopy-guided biopsy (CGB) in detecting high-grade cervical lesions and explore how human papilloma virus (HPV) integration status and other factors affect its performance. A retrospective cohort analysis involving 550 patients was conducted to evaluate whether the HPV integration plays a role in identifying high-grade cervical lesions and cervical cancer. Logistic regression models and area under the curve (AUC) calculations were employed. Our findings revealed that 53.5% of CGB/surgery pairs demonstrated congruent diagnoses, whereas 17.1% showed underestimation and 29.5% overestimation. Furthermore, multivariate logistic regression analysis identified several key predictors for cervical intraepithelial neoplasia (CIN)2+ and CIN3+ according to surgical pathology. Notably, a CGB confirming CIN2+ [odds ratio (OR)=6.0, 95% confidence interval (CI): 3.9-9.1, P<0.001], high-grade cytology (OR=2.6, 95% CI: 1.4-1.9, P=0.003), and HPV integration positivity (OR=2.2, 95% CI: 1.3-3.5, P<0.001) emerged as significant factors for CIN2+. Similarly, for CIN3+ identification, CGB confirming CIN2+ (OR=5.3, 95% CI: 3.4-8.3, P<0.001), high-grade cytology (OR=2.6, 95% CI: 1.5-4.7, P=0.001), and HPV integration positivity (OR=2.0, 95% CI: 1.3-3.1, P=0.003) were independent predictors. Our study highlights the innovative role of HPV integration testing as a pivotal adjunct to CGB and cytology, offering a comprehensive approach that may enhance the diagnostic precision for high-grade cervical lesions, ultimately achieving more precise management strategies.

Traditional Chinese Medicine Erhuang Suppository for Treatment of Persistent High-risk Human Papillomavirus Infection and Its Impact on Transcriptome of Uterine Cervix

High-risk human papillomavirus (HR-HPV) infection is the chief cause of cervical intraepithelial neoplasia (CIN) and cervical carcinoma. The Erhuang suppository (EHS) is a traditional Chinese medicine (TCM) prepared from realgar (As In this study, we evaluated the therapeutic efficacy of EHS in a randomized controlled clinical trial with a 3-month follow-up. Totally, 70 patients with persistent HR-HPV infection were randomly assigned to receive intravaginal administration of EHS or placebo. HPV DNA, ThinPrep cytologic test (TCT), colposcopy, and safety evaluation were carried out after treatment. Microarray analysis was performed to compare transcriptome profiles before and after EHS treatment. A K14-HPV16 mouse model was generated to confirm the efficiency of EHS. After 3 months, 74.3% (26/35) of the patients in the treatment group were HPV negative, compared to 6.9% (2/29) in the placebo group. High-throughput microarrays revealed distinct transcriptome profiles after treatment. The differentially expressed genes were significantly enriched in complement activation, immune response, and apoptotic processes. The K14-HPV16 mouse model also validated the remarkable efficacy of EHS. This study demonstrated that EHS is effective against HR-HPV infection and cervical lesions. Additionally, no obvious systemic toxicity was observed in patients during the trial. The superior efficacy and safety of EHS demonstrated its considerable value as a potential cost-effective drug for the treatment of HPV infection and HPV-related cervical diseases.

EZH2 Contributes to Anoikis Resistance and Promotes Epithelial Ovarian Cancer Peritoneal Metastasis by Regulating m6A

Histone modification has a significant effect on gene expression. Enhancer of zeste homolog 2 (EZH2) contributes to the epigenetic silencing of target chromatin through its roles as a histone-lysine N-methyltransferase enzyme. The development of anoikis resistance in tumor cells is considered to be a critical step in the metastatic process of primary malignant tumors. The purpose of this study was to investigate the effect and mechanism of anoikis resistance in ovarian adenocarcinoma peritoneal metastasis. In addition to examining EZH2 protein expression in ovarian cancer omental metastatic tissues, we established a model of ovarian cancer cell anoikis and a xenograft tumor model in nude mice. Anoikis resistance and ovarian cancer progression were tested after EZH2 and N6-methyladenosine (m6A) levels were modified. EZH2 expression was significantly higher in ovarian cancer omental metastatic tissues than in normal ovarian tissues. Reducing the level of EZH2 decreased the level of m6A and ovarian cancer cell anoikis resistance in vitro and inhibited ovarian cancer progression in vivo. M6a regulation altered the effect of EZH2 on anoikis resistance. Our results indicate that EZH2 contributes to anoikis resistance and promotes ovarian adenocarcinoma abdominal metastasis by m6A modification. Our findings imply the potential of the clinical application of m6A and EZH2 for patients with ovarian cancer.

Efficacy of Bispecific Antibody Targeting EpCAM and CD3 for Immunotherapy in Ovarian Cancer Ascites: An Experimental Study

This study aimed to explore the value of M701, targeting epithelial cell adhesion molecule (EpCAM) and CD3, in the immunotherapy of ovarian cancer ascites by the in vitro assay. The expression of EpCAM in ovarian cancer tissues was analyzed by databases. The EpCAM expression and immune cell infiltration in different foci of ovarian cancer were detected by 8-channel flow cytometry. The toxic effect of M701 on OVCAR3 was tested using the in vitro cytotoxicity assay. The 3D cell culture and drug intervention experiments were performed to evaluate the therapeutic effect of M701 in ovarian cancer specimens. Flow cytometry was used to examine the effect of M701 on the binding of immune cells to tumor cells and the activation capacity of T cells. The results of the bioinformatic analysis showed that the expression of EpCAM in ovarian cancer tissue was significantly higher than that in normal ovarian tissue. The 8-channel flow cytometry of clinical samples showed that the EpCAM expression and lymphocyte infiltration were significantly heterogeneous among ovarian cancer patients and lesions at different sites. The in vitro experiment results showed that M701 had a significant killing effect on OVCAR3 cells. M701 also obviously killed primary tumor cells derived from some patients with ovarian cancer ascites. M701 could mediate the binding of CD3 M701 showed significant inhibitory activity on tumor cells derived from ovarian cancer ascites, which had a promising application in immunotherapy for patients with ovarian cancer ascites.

Oncological and Reproductive Outcomes of Fertility-sparing Surgery in Women with Early-stage Epithelial Ovarian Carcinoma: A Multicenter Retrospective Study

With delayed childbearing in women, preservation of fertility is an important issue for reproductive-age patients with epithelial ovarian carcinoma (EOC). Fertility-sparing surgery (FSS) can be considered in patients with early-stage disease in order to preserve fertility and improve quality of life. In order to evaluate oncological safety, attitudes toward childbearing and reproductive outcomes in women with EOC who underwent FSS, this multicenter retrospective study was conducted. Between January 2005 and December 2014, total of 87 young women with FIGO stage I EOC were included, with their clinicopathologic parameters in relation to disease-free survival (DFS) and overall survival (OS) assessed. Attitudes toward childbearing, ovarian function and fertility were studied in women undergoing FSS (n=36). As a result, in contrast to radical surgery, FSS did not affect prognosis by Kaplan-Meier curves (log-rank test; DFS: P=0.484; OS: P=0.125). However, two of the three recurrence cases and both death cases were in FSS group stage IC. All women undergoing FSS resumed regular menstrual periods after chemotherapy. Only 16 (44.44%) had tried to conceive, and 17 pregnancies occurred in 15 (93.75%) women. Among 20 women who did not attempt conception, the most common reason was not being married (70%), followed by already having children (15%). In summary, FSS is considered safe in young women with stage IA EOC. Regular menstruation and good obstetric outcomes can be achieved. This study also provides some insight into the attitudes and social factors regarding fertility in EOC patients.

Ultrasound Features Improve Diagnostic Performance of Ovarian Cancer Predictors in Distinguishing Benign and Malignant Ovarian Tumors

To determine whether ultrasound features can improve the diagnostic performance of tumor markers in distinguishing ovarian tumors, we enrolled 719 patients diagnosed as having ovarian tumors at Nanfang Hospital from September 2014 to November 2016. Age, menopausal status, histopathology, the International Federation of Gynecology and Obstetrics (FIGO) stages, tumor biomarker levels, and detailed ultrasound reports of patients were collected. The area under the curve (AUC), sensitivity, and specificity of the bellow-mentioned predictors were analyzed using the receiver operating characteristic curve. Of the 719 patients, 531 had benign lesions, 119 had epithelial ovarian cancers (EOC), 44 had borderline ovarian tumors (BOT), and 25 had non-EOC. AUCs and the sensitivity of cancer antigen 125 (CA125), human epididymis-specific protein 4 (HE4), Risk of Ovarian Malignancy Algorithm (ROMA), Risk of Malignancy Index (RMI1), HE4 model, and Rajavithi-Ovarian Cancer Predictive Score (R-OPS) in the overall population were 0.792, 0.854, 0.856, 0.872, 0.893, 0.852, and 70.2%, 56.9%, 69.1%, 60.6%, 77.1%, 71.3%, respectively. For distinguishing EOC from benign tumors, the AUCs and sensitivity of the above mentioned predictors were 0.888, 0.946, 0.947, 0.949, 0.967, 0.966, and 84.0%, 79.8%, 87.4%, 84.9%, 90.8%, 89.1%, respectively. Their specificity in predicting benign diseases was 72.9%, 94.4%, 87.6%, 95.9%, 86.3%, 90.8%, respectively. Therefore, we consider biomarkers in combination with ultrasound features may improve the diagnostic performance in distinguishing malignant from benign ovarian tumors.

Clinical Features of Oxaliplatin-induced Hypersensitivity Reactions in Chinese Patients: A Retrospective Multicenter Analysis

The characteristics of oxaliplatin-induced hypersensitivity reactions (HSRs) in Chinese patients were investigated to provide a reference for patients treated with oxaliplatin. The study reviewed the records of patients who developed oxaliplatin-induced HSRs in 17 hospitals from May 2016 to May 2017. We collected and analyzed the basic information, history of oxaliplatin administration and premedication treatments, chemotherapy cycles, HSR symptoms, and the management and outcomes of these patients. Oxaliplatin-induced HSRs were recorded in 137 patients who had been treated with oxaliplatin-containing regimens. Five different chemotherapy regimens were applied. The median infusion cycle when oxaliplatin-induced HSRs occurred was 7, and HSRs occurred during or shortly after oxaliplatin infusion. Most of the patients experienced grade 1 or grade 2 HSRs with mild symptoms of pruritis (49.64%), flushing (46.72%), chest discomfort (26.28%), and urticaria (25.55%). The majority of the patients completely recovered from HSRs following treatment with antihistamines and dexamethasone. Seven patients completed chemotherapy with oxaliplatin after the symptoms resolved with proper management. The results indicate that oxaliplatin-induced HSRs remain an important issue in safely and successfully fulfilling oxaliplatin-containing chemotherapy. Further studies are needed to analyze the risk factors and establish prophylaxis for such reactions.

Adjuvant Chemotherapy May Not Be Necessary for Women with Stage IC1 Epithelial Ovarian Cancer

To determine whether adjuvant chemotherapy improves the prognoses in women with stage IC1 epithelial ovarian cancer (EOC). All eligible women diagnosed with stage IC1 EOC from 2003 to 2019 in Tongji Hospital were included. Patient characteristics, tumor features, surgical types, and chemotherapeutic treatments were collected. Kaplan-Meier analysis and Cox regression analysis were performed to evaluate progression-free survival (PFS) and overall survival (OS). Of the 140 patients (median age: 47 years old), 13 patients did not receive chemotherapy, and 127 received adjuvant chemotherapy. Kaplan-Meier analysis indicated that adjuvant chemotherapy offered no obvious improvements in PFS or OS. Subgroup analysis was conducted to adjust for the significant difference in incomplete staging surgery between the two groups, and chemotherapy still showed no benefit for survival. Cox regression analysis indicated that incomplete staging surgery was a risk factor for a worse PFS and that adjuvant chemotherapy remained unrelated to the prognosis. The patients were further divided based on the National Comprehensive Cancer Network recommendations: patients for whom observation is optional and chemotherapy would not improve the prognosis; and patients for whom chemotherapy is recommended. The results showed that postoperative chemotherapy had little correlation with survival. Our study suggests that postoperative chemotherapy may be unnecessary for patients with stage IC1 EOC. According to our results, incomplete staging surgery is a significant risk factor for PFS.

Clinicopathologic Characteristics and Survival of Patients with Rare Malignant Ovarian Yolk Sac Tumors: A Population-based Analysis

Yolk sac tumors (YSTs) are rare malignant germ cell tumors that usually affect young females. To date, there have been few studies on YSTs. We evaluated the relationship between clinicopathologic characteristics of patients with ovarian YSTs and disease outcome based on Surveillance, Epidemiology, and End Results data. The Kaplan-Meier method and log-rank test were used to evaluate differences in survival rates. Data for 269 patients were analyzed. The incidence of YSTs among ovarian germ cell tumors (OGCTs) cases was 0.4%; median patient age was 22.0 years, and most tumors were unilateral. Patients presented with distant metastasis (37.5%), localized disease (49.1%), and regional spread (8.9%). American Joint Committee on Cancer stage was available for 13 patients (stage IA, n=2; stage IC, n=1; stage IIIA, n=1; stage IIIB, n=3; stage IIIC, n=2; and stage IV, n=4). Survival rates at 1, 3, and 5 years were 91.0%, 84.0%, and 83.2%, respectively, for overall survival (OS) and 92.0%, 85.4%, and 84.5%, respectively, for disease-specific survival (DSS). The 5-year OS and DSS of patients with ovary tumors were 91.5% and 92.9%, respectively, compared to 74.8% and 77.2%, respectively, for those with extra-ovarian spread (P50 years was associated with shorter OS and DSS (both P<0.001), whereas no associatios of OS and DSS were observed with pathologic grade (P=0.49 for OS and 0.52 for DSS). In summary, YSTs are typically unilateral, of a high grade, and localized to the ovary; extra-ovarian spread has a poor outcome, and postmenopausal women have worse prognosis than premenopausal women.

Distinct Side Population Cell Subtypes Have Different Stemness Levels in Human Ovarian Cancer Cells

The stemness of different side population (SP) cell subtypes in ovarian cancer cells was studied, and the heterogeneity of ovarian cancer stem cells was analyzed. The cisplatin-resistant human serous ovarian cancer cell line C13 was stained with the bisbenzimide Hoechst 33342. A flow cytometry-based fluorescence-activated sorting method was used to obtain lower-SP (LSP) cells, upper-SP (USP) cells, and non-SP cells (NSP) based on their sensitivity to the staining time and Hoechst dye concentration. The sphere-forming capability, expression levels of stem cell markers, resistance to high concentrations of cisplatin, and subcutaneous tumorigenicity in NOD/SCID mice of the different cell subtypes were evaluated. The C13 cells contained SP cells with stemness characteristics, and the LSP cell subtype expressed higher levels of stem cell markers, had higher in vitro sphere-forming capability, higher cisplatin resistance and higher in vivo subcutaneous tumorigenesis than USP cells (P<0.05). NSP cells had no stemness. In conclusion, different subtypes of ovarian cancer SP cells have different stemness levels, and ovarian cancer stem cells may be heterogeneous.

Dysregulated RUNX1 Predicts Poor Prognosis by Mediating Epithelialmesenchymal Transition in Cervical Cancer

Runt-related transcription factor 1 (RUNX1) has been proven to be over-expressed and vital in many malignancies. However, its role in cervical cancer is still unclear. Some online databases (Oncomine, GEPIA, UALCAN, LinkedOmics, and others) were used to explore the expression level, prognostic significance, and gene mutation characteristics of RUNX1 in cervical cancer. The protein levels of RUNX1 in cervical cancer were measured by immunohistochemistry (IHC). The functional changes of cervical cancer cells were measured in vitro after decreasing RUNX1. Bioinformatic results revealed that RUNX1 was upregulated in cervical cancer compared to normal tissues. Moreover, over-expression of RUNX1 was significantly correlated with cervical cancer patients' clinical parameters (e.g., individual cancer stages, patients' age, nodal metastasis status, and others). Meanwhile, functional enrichment analysis of RUNX1-related genes indicated that RUNX1 was mainly involved in the epithelial-mesenchymal transition (EMT) process in cervical cancer. Furthermore, RUNX1 may be upregulated by hsamiR-616-5p and hsa-miR-766 identified by miRDB, TargetScan, and miRWalk. Finally, RUNX1 was upregulated in cervical cancer compared to normal tissues by IHC in collected cervical cancer samples. The invasion and migration abilities of cervical cancer cells were significantly reduced by repressing EMT after knocking down RUNX1 in vitro. RUNX1 was highly expressed in cervical cancer, and upregulated RUNX1 could significantly promote the invasive abilities of cervical cancer cells by inducing EMT. Therefore, RUNX1 may be a potential biomarker for early diagnosis and targeted therapy of cervical cancer.

Bioinformatic and Experimental Analyses Reveal That KIF4A Is a Biomarker of Therapeutic Sensitivity and Predicts Prognosis in Cervical Cancer Patients

This study aims to investigate the expression, prognostic value, and function of kinesin superfamily 4A (KIF4A) in cervical cancer. Cervical cancer cell lines (Hela and SiHa) and TCGA data were used for experimental and bioinformatic analyses. Overall survival (OS) and progression free survival (PFS) were compared between patients with high or low KIF4A expression. Copy number variation (CNV) and somatic mutations of patients were visualized and GISTIC 2.0 was used to identify significantly altered sites. The function of KIF4A was also explored based on transcriptome analysis and validated by experimental methods. Chemotherapeutic and immunotherapeutic benefits were inferred using multiple reference databases and algorithms. Patients with high KIF4A expression had better OS and PFS. KIF4A could inhibit proliferation and migration and induce G

Aberrant Sialylation in Ovarian Cancer: Orchestrating Progression, Metastasis, and Therapeutic Hurdles

Ovarian cancer (OC), a highly lethal gynaecological malignancy, is often diagnosed at advanced stages, resulting in a poor prognosis. Sialylation, an important form of glycosylation, significantly contributes to the progression of various solid tumours, including OC. Aberrant sialylation promotes tumour progression and metastasis by altering the structure and function of glycoproteins. Although its role in several solid tumours is well documented, the role of abnormal sialylation in OC and its potential as a therapeutic target remain poorly understood. This review highlights sialylation as a key regulator of the progression, metastasis, and drug resistance of OC. A deeper understanding of altered sialylation can contribute to the identification of novel therapeutic strategies for OC.

Is There Re-staging Surgery Necessity for Borderline Ovarian Tumors

This study assessed the necessity of surgical re-staging in women with borderline ovarian tumors (BOTs) and evaluated the impact of complete surgical staging, lymphadenectomy, and omentectomy on disease recurrence and survival. We retrospectively reviewed the medical records of patients with BOTs. A total of 901 patients were eligible for inclusion in the study, and we evaluated some of the variables and clinical/surgical characteristics of the cases. The effects of the type of surgical procedure, surgical staging, and complete or incomplete staging on recurrence were calculated. The rates of disease-free survival, overall survival, and recurrence were compared according to complete surgical staging. A Cox regression analysis was performed to identify potential prognostic factors, and survival curves were constructed using the Kaplan-Meier method. The overall recurrence rate was 13.9%, and recurrence was comparable between the complete surgical staging group and the incomplete groups (P>0.05). The performance of complete surgical staging did not show an effect on long-term survival, and complete surgical staging, omentectomy, and lymphadenectomy had no effect on recurrence. In multivariate analyses, only radical surgery and adjuvant chemotherapy were risk factors for the recurrence of BOTs. Furthermore, we found that omentectomy led to a relatively low recurrence rate in patients with International Federation of Gynecology and Obstetrics (FIGO) stage > I (P=0.022). Our results suggest that complete surgical staging should be considered a standard treatment for patients with advanced stage BOTs but not for those at FIGO stage I. It might be safe to reduce the scope of surgical procedures in patients with early-stage BOTs. However, it is not necessary to perform re-staging operations for BOTs with a macroscopically normal extra-ovarian appearance.

A BRCA1 Splice Site Variant Responsible for Familial Ovarian Cancer in a Han-Chinese Family

Ovarian cancer (OC) is one of the most common and most lethal gynecological malignancies. OC has an age-dependent incidence and occurs more commonly in females older than 50 years old. Most OC patients are diagnosed at an advanced stage and have a poor prognosis. Germline mutations in the BRCA1 DNA repair associated gene (BRCA1) and the BRCA2 DNA repair associated gene (BRCA2) account for 20%-25% of epithelial ovarian cancer (EOC). BRCA1 germline mutations are more common in Chinese EOC patients. This study reported a three-generation Han-Chinese family containing four EOC patients and a rectal adenocarcinoma patient. Whole-exome sequencing was performed on two EOC patients and an unaffected individual. Variant validation was also performed in all available members by Sanger sequencing. A heterozygous splice site variant, c.4358-2A>G in the BRCA1 gene, was identified. Bioinformatic analysis showed that the variant may change the splicing machinery. The BRCA1 splice site variant, c.4358-2A>G was identified as the likely genetic cause for EOC, and may also be associated with the increased risk of rectal adenocarcinoma in the family. The findings were beneficial for genetic counseling, helpful for cancer prevention in other family members, and may facilitate therapy decision-making in the future to reduce cancer lethality.

Diagnostic Value of Circulating PIGF in Combination with Flt-1 in Early Cervical Cancer

The utility of placental growth factor (PlGF) and its receptor VEGFR-1 (Flt-1) as biomarkers for cervical cancer has not been clarified yet. To address this issue, we investigated the levels of soluble PlGF (sPlGF) and soluble Flt-1 (sFlt-1) in the serum from patients with early cervical cancer, cervical intraepithelial neoplasia (CIN) and controls in this study. sPlGF and sFlt-1 were detected in 44 preoperative patients with cervical cancer, 18 cases with CIN, and 20 controls by ELISA. It was found that both sPlGF and sFlt-1 were significantly increased in the cervical cancer group as compared with those in CIN and control groups. sPlGF presented a high diagnostic ability of cervical cancer, with a sensitivity of 61.36% and a specificity of 89.47%; and sFlt-1 with a sensitivity of 50.00% and a specificity of 92.11%. Importantly, the combined use of sPlGF and sFlt-1 could increase the diagnostic rate of cervical cancer, with a sensitivity of 70.45% and a specificity of 92.11%. These results indicated that both sPlGF and sFlt-1 in circulation can serve as possible valuable diagnostic biomarkers for cervical cancer, and the combined use of them can be more valuable to diagnose the patients with early cervical cancer.

Antitumor Effect of Apcin on Endometrial Carcinoma via p21-Mediated Cell Cycle Arrest and Apoptosis

Endometrial carcinoma (EC) is a prevalent gynecological malignancy characterized by increasing incidence and mortality rates. This underscores the critical need for novel therapeutic targets. One such potential target is cell division cycle 20 (CDC20), which has been implicated in oncogenesis. This study investigated the effect of the CDC20 inhibitor Apcin on EC and elucidated the underlying mechanism involved. The effects of Apcin on EC cell proliferation, apoptosis, and the cell cycle were evaluated using CCK8 assays and flow cytometry. RNA sequencing (RNA-seq) was subsequently conducted to explore the underlying molecular mechanism, and Western blotting and coimmunoprecipitation were subsequently performed to validate the results. Animal studies were performed to evaluate the antitumor effects in vivo. Bioinformatics analysis was also conducted to identify CDC20 as a potential therapeutic target in EC. Treatment with Apcin inhibited proliferation and induced apoptosis in EC cells, resulting in cell cycle arrest. Pathways associated with apoptosis and the cell cycle were activated following treatment with Apcin. Notably, Apcin treatment led to the upregulation of the cell cycle regulator p21, which was verified to interact with CDC20 and consequently decrease the expression of downstream cyclins in EC cells. In vivo experiments confirmed that Apcin treatment significantly impeded tumor growth. Higher CDC20 expression was observed in EC tissue than in nonmalignant tissue, and increased CDC20 expression in EC patients was associated with shorter overall survival and progress free interval. CDC20 is a novel molecular target in EC, and Apcin could be developed as a candidate antitumor drug for EC treatment.

ZNF554 Inhibits Endometrial Cancer Progression via Regulating RBM5 and Inactivating WNT/β-Catenin Signaling Pathway

Uterine corpus endometrial carcinoma (UCEC), a kind of gynecologic malignancy, poses a significant risk to women's health. The precise mechanism underlying the development of UCEC remains elusive. Zinc finger protein 554 (ZNF554), a member of the Krüppel-associated box domain zinc finger protein superfamily, was reported to be dysregulated in various illnesses, including malignant tumors. This study aimed to examine the involvement of ZNF554 in the development of UCEC. The expression of ZNF554 in UCEC tissues and cell lines were examined by qRT-PCR and Western blot assay. Cells with stably overexpressed or knocked-down ZNF554 were established through lentivirus infection. CCK-8, wound healing, and Transwell invasion assays were employed to assess cell proliferation, migration, and invasion. Propidium iodide (PI) staining combined with fluorescence-activated cell sorting (FACS) flow cytometer was utilized to detect cell cycle distribution. qRT-PCR and Western blotting were conducted to examine relative mRNA and protein levels. Chromatin immunoprecipitation assay and luciferase reporter assay were used to explore the regulatory role of ZNF554 in RNA binding motif 5 (RBM5). The expression of ZNF554 was found to be reduced in both UCEC samples and cell lines. Decreased expression of ZNF554 was associated with higher tumor stage, decreased overall survival, and reduced disease-free survival in UCEC. ZNF554 overexpression suppressed cell proliferation, migration, and invasion, while also inducing cell cycle arrest. In contrast, a decrease in ZNF554 expression resulted in the opposite effect. Mechanistically, ZNF554 transcriptionally regulated RBM5, leading to the deactivation of the Wingless (WNT)/β-catenin signaling pathway. Moreover, the findings from rescue studies demonstrated that the inhibition of RBM5 negated the impact of ZNF554 overexpression on β-catenin and p-glycogen synthase kinase-3β (p-GSK-3β). Similarly, the deliberate activation of RBM5 reduced the increase in β-catenin and p-GSK-3β caused by the suppression of ZNF554. In vitro experiments showed that ZNF554 overexpression-induced decreases in cell proliferation and migration were counteracted by RBM5 knockdown. Additionally, when RBM5 was overexpressed, it hindered the improvements in cell proliferation and migration caused by reducing the ZNF554 levels. ZNF554 functions as a tumor suppressor in UCEC. Furthermore, ZNF554 regulates UCEC progression through the RBM5/WNT/β-catenin signaling pathway. ZNF554 shows a promise as both a prognostic biomarker and a therapeutic target for UCEC.

Adjuvant Chemotherapy versus Radiotherapy in High-risk, Early-stage Endometrioid Endometrial Carcinoma

The present study was designed to evaluate the effects of adjuvant chemotherapy (CT) vs. radiotherapy (RT, alone or combined with CT) on the prognosis of patients with high-risk, early-stage (stage I and stage II) endometrioid endometrial carcinoma. This single-center retrospective clinical study was conducted in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between 2010 and 2019. In the present study, endometrioid endometrial carcinoma patients, who underwent total hysterectomy and bilateral salpingo-oophorectomy followed by postoperative adjuvant CT or RT (alone or combined with CT), and were diagnosed with stage IA grade 2/3 with lymph-vascular space invasion (LVSI), and stage IB with two or more uterine risks, including old age, histological grade 2 or 3, LVSI and stage II, were included. According to the postoperative adjuvant therapy, all eligible patients were divided into two groups: CT group and RT (RT±CT) group. The primary objective was to investigate overall survival (OS) and disease-free survival (DFS) between the CT and RT groups. Grade 3 or worse adverse events were also presented in the present study. A total of 145 eligible patients were included. Among these patients, 97 patients underwent adjuvant CT and 48 patients underwent adjuvant RT (RT±CT). The median follow-up was 47.2 months, and the five-year OS rate was 92.7% in the CT group and 88.6 % in the RT group [hazard ratio (HR): 0.81, 95% confidence interval (CI): 0.22-2.99). The 5-year DFS rate for the two groups was 85.7% and 80.2%, respectively (HR: 0.82, 95% CI: 0.33-2.05). The cumulative incidence of local-regional disease recurrence at 60 months of follow-up was 6.2% in the CT group and 6.3% in the RT group (HR=1.11; 95%CI: 0.28-4.35). The cumulative incidence of distant recurrence at 60 months of follow-up was 5.2% in the CT group and 10.4% in the RT group (HR=0.65; 95%CI: 0.19-2.24). Both groups of patients were well-tolerant, and the only grade 3 or worse adverse events were neutropenia and thrombocytopenia. There was no difference in efficacy for adjuvant CT or adjuvant RT (RT±CT) in high-risk, early-stage endometrioid endometrial carcinoma. CT exhibited a trend of reducing the distant relapse, although there was no significant difference, when compared with adjuvant RT (RT±CT).