Clinical Laboratory

Analysis of a Near-Missing RhDV Type 1 Detection

The safety of blood transfusion can be significantly affected by complex blood group antigens, especially the polymorphic Rh blood group system. This case study is to alert clinicians and laboratory personnel to accurately identify and manage RhD blood groups. A Chinese female patient with cervical squamous cell carcinoma underwent surgical treatment; her blood typing identified that she had serological type A and different RhD titers to the anti-D reagent. RHD genetic testing was performed. After RHD gene sequencing, the patient was confirmed as RhDV Type 1; 1.5 units of type A RhD-negative suspended red blood cells were transfused to the patient, and the hemoglobin level increased from 66 to 73 g/L. No adverse reaction occurred, and the patient recovered well after surgery. RhD antibody reagents from different manufacturers are required to identify the RhD subtypes and ensure transfusion safety.

A Rare Case of Intraoperative Transfusion-associated Hypotension in a Chinese Pregnant Patient

Transfusion-associated hypotension (TAH) is characterized by the abrupt onset of hypotension immediately after the start of transfusion and usually resolves when transfusion ceases. The pathogenesis of TAH is not yet fully understood. A 36-year-old woman underwent exploratory laparotomy and cesarean section due to cervical squamous cell carcinoma. During surgery, the patients experienced acute, profound intraoperative hypotension within 5 minutes after the initiation of the prestorage leukocyte-reduced suspension red blood cells (RBC) transfusion. A series of laboratory tests confirmed TAH. The patient then underwent a successful blood transfusion and operation. TAH can occur in all types of blood components under various conditions. The literature surrounding the incidence of TAH differs widely from 0.03 to 2.13 in 10,000. This is the first case report of TAH in an intraoperative pregnant woman in China, neither associated with prestorage leukocyte-reduced RBC nor irrelevant to ACE inhibitors. Some biological response mediators (BRMs) and acute phase reactive proteins might play a role in this case. Understanding the etiology and the pathophysiology of TAH facilitates proper management, leading to improved transfusion safety.

Hyperproteinemia, Hematuria, and Squamous Cell Shedding in Elderly Cervical Cancer Patients and the Potential Alternative Screening Tool

In Saudi Arabia, cervical cancer, frequently caused by human papillomavirus (HPV) infection, is a common cancer. The usual procedures for screening and diagnosing cervical cancer include Pap smears and HPV tests, even though they have considerable drawbacks, particularly for older women (> 60 years) who have limited access to or compliance with these tests. Urinalysis is a simple, noninvasive test that has been suggested as an alternative procedure. This study aimed to investigate the change in urinalysis characteristics in cervical cancer patients in elderly females and the possible use of urinalysis as a screening or diagnostic tool for cervical cancer in older women. This was an exploratory cross-sectional study of 190 cervical cancer patients diagnosed between January 2018 and August 2021. Based on age, the study included two groups, < 60 years and ≥ 60 years. Urinalysis characteristics, including bacterial count, blood level, protein level, and squamous epithelial cell shedding, were compared between the age groups by using the chi-squared and Kruskal-Walli tests. The results showed a significant difference between aged females and younger females with cervical cancer at the blood level, protein level, and squamous epithelial cell shedding in the urine. The older women (≥ 60 years) had higher incidences of increased bacterial count, blood levels, protein levels, and squamous epithelial cell shedding than the younger women (< 60 years). The main finding of the study implies that there are significant changes in urine characteristics in cervical cancer patients including hyperproteinemia, hematuria, and squamous cell shedding in elderly patients compared to younger patients, and it proposes a potential role for urinalysis as a screening tool for cervical cancer in older women. Urinalysis could be a potential screening tool for cervical cancer in older women who have not been screened or have no screening access. Further studies are needed to validate these findings.

Assessing the Accuracy of Self-Specimen Collection in HPV Testing: Implications for Clinical Laboratory Practice

Prevalence and Genotype Distribution of HPV in Hangzhou, China

For women, cervical cancer is the most prevalent cancer and the most common cause of cancer-related deaths worldwide. Human papillomavirus (HPV) is causatively linked to over 90% of cervical cancer cases. Our retrospective study explored the clinical and laboratory data of outpatients with HPV infection to analyze the prevalence and genotype distribution of 3,793 outpatients in the Hangzhou area by using HPV genotype tests. It could provide value for an effective prevention and treatment of HPV infection. In total, 3,793 female outpatients were randomly selected from January 2022 to December 2023. Exfoliated cervical cells were collected using a cytobrush and HPV genotype screening was conducted for testing. Data of all outpatients were collected from the hospital's electronic medical records, and SPSS 26.0 software was used to perform the statistical analysis. Out of 3,793 outpatients, 953 were detected as positive, and the positive rate was 25.13%. The age of the outpatients ranged from 15 - 97, with an average age of 39.91. All outpatients were divided into six age groups. Among the six age groups, the HPV positive rates were, with ascending age, 43.90%, 33.27%, 21.49%, 16.99%, 27.30%, and 25.48%, and the highest positive rate was observed in those aged  20 with a rate of 43.90%. There were significant differences in the positive rates among different age groups (p < 0.05). There were more outpatients with a single infection than with multiple infection (p < 0.05). The positive rate of single infection was the highest in the 31 - 40 and 41 - 50 age groups (74.32% for both) and the positive rate of multiple infection was the highest in the  20 age group (66.67%). Among 24 genotypes, HPV 52, 58, and 51 were the most commonly detected. All three were high-risk genotypes, and HPV 52 was the most dominant in all age groups. As distribution according to quarter, more HPV infection occurred in the fourth quarter, which had a significant difference (p < 0.05). And in the first quarter, the number of HPV positive infections was the lowest. Prevalence and genotype distribution of HPV in the Hangzhou area were different from those of other regions. More single infection, and more multiple infection occurring in low age and in the fourth quarter were the characteristics of HPV infection in the Hangzhou area. It was suggested that vaccine containing HPV 52 might be a better choice for this region.

Circ-HMGCS1, an Indicator of Survival and Prognosis in Cervical Cancer Patients

The aim was to investigate circ-HMGCS1 expression and its correlation with clinical features and survival in cervical cancer (CC) patients. This prospective study recruited 100 patients with CC who underwent surgical resection. Circ-HMGCS1 expression was measured by RT-qPCR. Disease-free survival (DFS) and overall survival (OS) were recorded. Circ-HMGCS1 was upregulated in tumor tissues and had a good value in separating tumor tissues from normal tissues. Circ-HMGCS1 expression in tumor tissues was positively correlated with tumor size, lymph node metastasis, and FIGO stage. High circ-HMGCS1 expression predicted worse DFS and OS. circ-HMGCS1 serves as an indicator of survival and prognosis in CC patients.

Diagnostic Value of lncRNA ROR in Differentiating Ovarian Cancer Patients

The current study aims to investigate the prognostic value of long non-coding RNA (lncRNA) ROR in ovarian cancer patients. Sixty cases of ovarian cancer patients were collected from January 2017 to December 2017. The expression of lncRNA ROR in the plasma and tissues of ovarian cancer was detected by RT-qPCR. The relationship between the expression of lncRNA ROR and the clinicopathological characteristics was analyzed. The expression of lncRNA ROR in the plasma of ovarian cancer patients was significantly higher than that in healthy controls. Compared with that in the adjacent non-cancerous tissues, the level of lncRNA ROR was significantly enhanced in the ovarian cancer tissues. Further study showed that the expression of lncRNA ROR was closely related to FIGO stage, tumor grade, and lymph node metastasis. Pearson's correlation assay indicated that lncRNA ROR positively correlated with CA125 in ovarian cancer patients. Moreover, the combined detection of plasma lncRNA ROR and CA125 had the highest value in the diagnosis of ovarian cancer compared to that of lncRNA ROR or CA125 alone. The enhanced level of plasma lncRNA ROR could be used as a potential biomarker for the diagnosis of ovarian cancer.

Investigation and Follow-up of HPV Infection on Married Mongolian Women in Hulunbuir

The aim of the study was to determine the high-risk factors of Mongolian human papillomavirus (HPV) infection in Hulunbuir area and to explore the guiding role of HPV16 viral load change in the treatment of cervical intraepithelial neoplasia 1 (CIN 1). The HPV qualitative results of 963 married women of Mongolian nationality aged 21 - 65 were screened using real-time PCR in the Hulunbeir area, logistic analysis statistics was used to judge the high-risk factors of infection, and the χ2 test was the analysis method of the count data; hybrid capture was used. II technology was used to detect the changes of HPV DNA content of CIN I outpatients before treatment, 6, 12, and 18 months after treatment. At the same time the change trend of vaginal secretions and thinprep cytologic test (TCT) was observed. The measurement data between the two groups by was compared using t-test. The positive rate of HPV infection was 22.31% in Mongolian married women in Hulunbuir area. Drinking habits and the number of sexual partners were the common infection factors of all high-risk types. Infection factors of HPV16, 18, and other high-risk types also included number of marriages. There was a significant difference between the content of HPV DNA in CIN I patients before treatment and the two groups at 12 and 18 months after treatment (p < 0.05). The number of patients with degree III or IV of cleanliness and TCT showed that the number of patients with low-grade atypical hyperplasia decreased with the treatment time, which was consistent with the change of HPV DNA content. In the Hulunbuir area, the number of Mongolian women with HPV infection is higher than that of the Han nationality, so we should strengthen the popularization and propaganda of the knowledge about HPV infection in the Mongolian population settlement. The change of DNA content of high-risk HPV can be used as the observation index of CIN I treatment evaluation.

Human Papillomavirus (HPV) Prevalence, Temporal Dynamics and Association with Abnormal Cervical Cytology Findings in Women from Croatia: Is there a Compounding Effect of Low-Risk/High-Risk HPV Co-Infection?

Human papillomavirus (HPV) is a major risk factor for cervical dysplasia and invasive cervical cancer; therefore, regular screening by cervical smear cytology or HPV testing is recommended. We aimed to determine the overall and risk group-specific HPV prevalence, age distribution, and temporal trends and to appraise the correlation of HPV positivity with abnormal cervical cytological findings. This retrospective, single-center study involved a total of 751 women (aged 18 - 67) concurrently subjected to HPV DNA testing and cervical cytology evaluation over a 10-year period in Zagreb, Croatia. Digene HC2 HPV DNA test (Qiagen Corporation, USA) was employed in screening specimens for both low-risk and high-risk HPV risk groups. The cytology was reported using the Bethesda system and in accordance with uniform classification of uterine cervix cytological findings in Croatia "Zagreb 2002". Statistical significance was set at p < 0.05. The overall HPV prevalence in our study population was 48.6%, and the 18 - 30 age group presented with the highest infection burden (p = 0.046). A decrease in low-risk and high-risk mono-positivity has been observed over the 10-year period; conversely, there was a significant increase in low-risk/high-risk co-positivity (p = 0.007). Low-risk/high-risk HPV co-infection resulted in a compounding effect which increased the occurrence of abnormal cells, HPV-associated changes and low grade squamous intraepithelial lesions (LSIL/cervical intraepithelial neoplasia grade I) in cervical cytology when compared to mono-infection with either low-risk or high-risk HPV. On the other hand, such effect has not been demonstrated for high grade squamous intraepithelial lesions (HSIL/ cervical intraepithelial neoplasia grades II and III). The overall HPV prevalence in female outpatients was high, underscored with rising co-positivity rates. Such co-infection with both low-risk and high-risk HPV (predominantly seen in women younger than 30) can exhibit a compounding effect in the occurrence of cytological abnormalities and low grade squamous intra-epithelial lesions (LSIL), which has to be considered in future diagnostic and screening algorithms.

Application Value of Detection of High-Risk HPV Infection in Early Cervical Cancer Patients in Disease Diagnosis and Prognosis Evaluation

To analyze the relationship between HPV infection and early cervical cancer and postoperative survival outcomes. A total of 556 women were recruited to receive TCT and HPV tests from October 2017 to October 2018. The type of disease was pathologically diagnosed. The HPV positive rate, HPV-DNA, and E6/E7 mRNA quantitative level were detected, and the diagnostic accuracy of the subjects was analyzed by the receiver operating characteristic (ROC). The cervical intraepithelial neoplasia (CIN) and early cervical cancer patients were radically cured and followed up for 12.0 months to analyze the recurrence rate. Seventy-two cases of chronic cervicitis, 54 cases of CIN, and 51 cases of cervical cancer patients were pathologically diagnosed (32 cases in early stage and 19 cases in middle and late stage). HPV positive rate increased gradually in chronic cervicitis, CIN, and cervical cancer group (p < 0.001) and HPV 16 + 18 subtype. The positive rate was significantly different (p = 0.009). HPV-DNA and E6/E7 mRNA quantification also showed significant differences (p < 0.001). ROC analysis indicated that the accuracy of HPV-DNA and E6/E7 mRNA quantitative diagnosis of malignant lesions (CIN+ cervical cancer) were 0.865 and 0.879, respectively. There were 4 cases (7.41%) of recurrence in CIN group and 5 cases (15.63%) in early cervical cancer group. There was no difference (p = 0.401) among all of the patients. All patients with recurrence were HPV positive. HPV detection is an indispensable screening method for early cervical cancer and precancerous lesions, and comprehensive HPV 16 and 18 subtypes. DNA and E6/E7 mRNA quantification assay would further improve the accuracy of screening.

Diagnostic Value of Serum N1-Methylnicotinamide in Cervical Cancer Patients

The current study evaluated the level of serum N1-methylnicotinamide (me-NAM) in cervical cancer patients and further explored whether serum me-NAM was related to the prognosis of cervical cancer. Fifty-eight cases of cervical intraepithelial neoplasia patients, 78 cases of cervical cancer patients, and 52 healthy women were included in the present study. Serum me-NAM concentrations were determined by liquid chromatography with tandem mass spectrometry. Receiver operating characteristic (ROC) curve was used to assess me-NAM as a biomarker and Kaplan-Meier analysis was carried out to evaluate the survival rate. Our data showed that the level of serum me-NAM in cervical cancer patients was significantly higher than that in the cervical intraepithelial neoplasia group and the healthy control group. Furthermore, the level of me-NAM in cervical cancer tissues of stage I, II, III, and IV was higher than that of those without lymph node metastasis. The area under the receiver operating characteristic curve (ROC) for me-NAM was higher than that of squamous cell carcinoma antigen (SCC Ag) and carbohydrate antigen 125 (CA125) when comparing cervical cancer from CIN or healthy control. The combination of me-NAM and SCC Ag or CA125 could improve the diagnostic efficiency better than SCC Ag or CA125 alone. Compared with me-NAM low expression group, the survival rate and time of me-NAM high expression group were lower and shorter. Altogether, elevated serum me-NAM levels contribute to the progression of cervical cancer and may be used as a marker for the prognosis of patients with cervical cancer.

Increased ADAM12 Expression Predicts Poor Prognosis in Cervical Cancer Patients before General Anesthesia

The current study aims to investigate the expression and diagnostic value of ADAM12 in patients with cervical cancer before general anesthesia. Seventy-eight cases of cervical cancer patients were included in the present study. RT-PCR and western blot were used to detect the expression of ADAM12 in cervical cancer tissues and adjacent tissues. Meanwhile, the expression of secretory ADAM12 in serum of cervical cancer patients and healthy people was detected by ELISA. The relationship between ADAM12 expression and prognosis of cervical cancer patients was analyzed. ROC analysis was carried out to explore the diagnostic value of ADAM12. Our data showed that the expression of ADAM12 mRNA and protein in cervical cancer tissues was significantly up-regulated compared with the adjacent tissues. ELISA assay showed that the content of ADAM12 in serum of cervical cancer patients was significantly higher than that of healthy people. Furthermore, ADAM12 expression was closely related to tumor invasion, TNM stage, lymph node metastasis and tumor differentiation. Kaplan-Meier survival analysis showed that the overall survival rate of patients with high ADAM12 was significantly lower than that of patients with low ADAM12 expression. The AUC of ADAM12, CEA, CA125, and SCC for cervical cancer was 0.893, 0.510, 0.769 and 0.550, respectively, while the highest value of AUC was 0.946 by the combination of the four indexes. In summary, increased expression of ADAM12 in cervical cancer patients can be used as an independent prognostic marker.

The Frequency and Typing of HPV Virus Among Suspected Women Referred to HPV Genotyping Test in Mazandaran, Northern Iran

Human papilloma viruses are a group of the Papillomaviridae family (ds DNA viruses), which infect basal epithelial cells. So far, 228 types of HPV have been identified, in which about 40 types infect the genital mucosa. In Iran, cervical cancer has been reported as the second most common malignancy in women which is approximately 8.8% of all cancers in women. HPV genotypes are classified as high-risk and low-risk according to cervical cancer. According to previous reports, nearly 70% of cervical cancers occur by HPV genotypes 16 and 18, of which genotype 16 is known as the most prevalent type. The main goal of this study was determining the frequency of HPV virus and its genotypes in the female population of Mazandaran. This study was performed on 91 pathological samples. DNA was extracted from 500 μL of liquid-based cytology samples and PCR was performed for all of the samples. Genotyping step was performed based on strip assay method. HPV 39 (6.55%), 56 (3.27%), 51 (3.27%), and 68 (3.27%) were the most frequent types respectively. Also, HPV 11 (8.19%) and 6 (3.27%) show the most frequency among LR-HPV genotypes. HPV type 6 (16.39%), 56 (14.75%), 11 (14.75%), 16 (13.11%), and 66 (11.47%) were the four most common types seen in mixed infection samples. Differences among the types of HPV can be due to various geographical distributions of HPV. Our results revealed HPV 39 (6.55%) is the most common type among of HR-HPV followed by HPV 56, 51, 68 (3.27%); however, HPV 16 and HPV 18 were seen in just one case. HPV 11 (8.19%) and HPV 6 (3.27%) were the most common type among of LR-HPV.

Deep Vein Thrombosis in Pelvic Tumor Patients: Correlating Serum Coagulation Factors with Clinical Risk Profiles

Pan-Cancer Bioinformatics Analysis of Matrix Metalloproteinase-9 (MMP9)

Clinical Observation and Analysis of Transient Postoperative CA-125 Elevation in a Patient with Sigmoid Colon Adenocarcinoma

Identification of Endoplasmic Reticulum Stress-Related Gene Signature Reveals KRT8 as a Target in Ovarian Cancer

Ovarian cancer (OC) is an invasive gynecological cancer with an overall 5-year survival rate of less than 45%. Endoplasmic reticulum (ER) stress plays a crucial role in regulating oncogenic events and immune-modulatory pathways, influencing malignant progression, antitumor immunity, and treatment response. However, the full scope of ER stress in ovarian cancer remains poorly understood and warrants further investigation. RNA sequencing and clinical data were sourced from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus database (GEO). ER stress-related genes associated with ovarian tumor prognosis were identified, and an ER stress risk score model was developed using LASSO regression. We utilized this ER stress risk score to explore differences in immune cell infiltration. Furthermore, the biological role and expression of the risk gene KRT8 were validated through molecular biology experiments. We identified 573 genes related to ER stress that were differentially expressed genes (DEGs) between normal and tumor tissues. The ER stress-related risk signature (ERRS) constructed using the TCGA dataset was regarded as an independent and significant prognostic model for predicting cancer progression and instructing clinical decisions. Additionally, KRT8 was found to be overexpressed in ovarian cancer cells and tissues. Downregula-tion of KRT8 inhibited ovarian cancer cell proliferation and migration (in both SKOV3 and OVCAR8 cells) in vitro. The ER stress-related gene model we developed can be utilized to assess the prognostic risk for OC patients. Importantly, KRT8 was identified as a key risk gene in ovarian cancer, promoting tumor progression, and holds potential as a novel therapeutic target.

Immune Cells and Risk of Cervical Cancer: Evidence from a Mendelian Randomization Study

Immune dysfunction is involved in the development of cervical cancer. There is lack of causal evidence presenting the effects of immune cells on the risk of cervical cancer (CC). The genetic information of single nucleotide polymorphisms (SNPs) from European descents was employed and a two-sample Mendelian randomization (MR) strategy was designed. In total, 731 kinds of immune cells were included as the exposures. For cervical cancer, the data was from the cohort involving almost 24,0000 participants. The inverse variance weighted (IVW) approach served as the main strategy for causality inference. MR-Egger and weighted median were the alternative methods for comparison. Sensitivity analyses focusing on heterogeneity and pleiotropy were then carried out to verify the estimated effects. After selecting eligible SNPs for MR analysis, the IVW approach identified a total of 24 immune cell characteristics which were causally correlated with CC at p < 0.05. Among them, six immune cell phenotypes are confirmed to be related to an elevated risk of CC, while the remaining eighteen immune cell characteristics demonstrate protective effects against CC. MR-Egger and weighted median showed comparable results, and the detected associations passed the heterogeneity and pleiotropy tests. This Mendelian randomization study demonstrated causal associations between immune cells and CC, underscoring the intricate interactions of the immune system with CC. The results also provide insights into the mechanisms of CC development attributed to immunological regulation and highlight potential therapeutic targets for improving immune responses in patients with CC.

Thromboelastography Parameters Change Significantly in Patients with Endometrial Cancer and Uterine Fibroids

The goal was to clarify the changes of TEG parameters in patients with uterine fibroids and endometrial cancer and the clinical diagnostic values of TEG parameters. A total of 57 patients with uterine fibroids and 43 patients with endometrial cancer were included, and their TEG parameters were analyzed and compared with 45 healthy women. Routine coagulation indicators were also collected and compared. For significantly changed TEG indicators, the ROC curves were used to evaluate their diagnostic efficacy and determine the cutoff values. The TEG indicators of patients with endometrial cancer of stag I and II were also compared. APTT, and PT levels in endometrial cancer patients were significantly shorter than those in healthy controls. FIB level in endometrial cancer patients were significantly higher than those in healthy controls. Angle, MA, CI, E, G, and TPI levels were significantly upregulated in endometrial cancer patients while TMA was significantly decreased. According to ROC curve analysis, G and E had a good auxiliary diagnostic efficiency for the detection of uterine fibroids (cutoff value 6,691 d/sec and 133.8 d/sec) and TPI has good sensitivity and specificity for the diagnosis of endometrial cancer (cutoff value 51.3 dyn/cm2). The TEG index of patients with stage I and II endometrial cancer did not reach statistical difference. Thromboelastography parameters change significantly in patients with endometrial cancer and uterine fibroids.

Next Generation Sequencing is a Reliable Tool for Detecting BRCA1/2 Mutations, Including Large Genomic Rearrangements

Next-generation sequencing (NGS) has been implemented as a rapid and cost-effective BRCA1/2 test strategy. The Oncomine™ BRCA Research Assay is an NGS-based tool for simultaneous detection of small-scale mutations and large genomic rearrangements (LGRs). We evaluated this NGS assay using different versions of Ion Reporter™ (IR) software. A total of 258 patients with breast, ovarian, primary peritoneal, and fallopian tube cancer, or a family history thereof, were enrolled in the study. The NGS assay was implemented for all samples, and the results were compared with those of Sanger sequencing and MLPA. All small-scale variations in Sanger sequencing were successfully detected by NGS assay. For the detection of LGRs, this assay showed 100% sensitivity from IR v5.10, and the latest version of the software (v5.16) showed the highest sensitivity and specificity. NGS with an appropriately updated workflow proved reliable for comprehensive BRCA1/2 gene testing, including LGR screening, which could facilitate efficient and accurate decision-making regarding treatment.

The Role of Prophylactic Application of Granulocyte Colony Stimulating Factor in Adjuvant Chemotherapy for Epithelial Ovarian Cancer

The goal of this study was to investigate the relative merits of granulocyte colony stimulating factor (G-CSF) prophylaxis for patients with epithelial ovarian cancer (EOC). The Institutional Review Board of the Women's Hospital, Zhejiang University School of Medicine has approved this study (No. IRB-20200132-R) with a waiver of informed consent. Patients with EOC who received the combination of a platinum drug and paclitaxel (TP) chemotherapy regimens in the hospital from January 1, 2016, to November 30, 2020, were included in this retrospective cohort study. To assess clinical effectiveness, patients were categorized into groups who received either long-acting G-CSF or short-acting G-CSF prophylaxis with and without prophylaxis. The incidence of neutropenia and adverse events were compared between groups. All results of chemotherapy were pooled for analysis. Of the identified cases, 128 patients were evaluated. Long-acting G-CSF and short-acting G-CSF were applied in 51 and 41 patients, respectively. The absolute neutrophil count at the nadir was significantly lower in patients with G-CSF prophylaxis than those without G-CSF (p = 0.001). The duration of ANC levels < 2.0 x 109/L in cycles using short-acting G-CSF was longer than that in those receiving long-acting G-CSF (p = 0.045). There were no serious adverse events observed in patients with G-CSF. No significant differences in the incidence of febrile neutropenia (FN) and duration of grade 2 - 4 neutropenia were observed between groups receiving G-CSF prophylaxis and those without. Primary prophylaxis with G-CSF in chemotherapy for epithelial ovarian cancer appears to be of low value in terms of its relationship to the incidence of FN and prognosis.

Mutations of BRCA1/2 Genes in the West of Turkey and Genotype-Phenotype Correlations

Mutations of the BRCA1/2 genes are associated with increased breast and ovarian cancer. The aim of this study was to investigate the founder mutations of the BRCA1 and BRCA2 genes in the Turkish population in the Aegean region as well as their genotype-phenotype correlations. All the patients were provided with BRCA1/2 testing criteria according to the National Comprehensive Cancer Network. QIAseq Targeted DNA Panels were used for the BRCA1/2 coding regions. Of the 181 studied patients, 38 (21%) were found to carry pathogenic or likely pathogenic mutations, while 20 (11%) patients were found to carry variants of unknown significance. The most common pathogenic mutations were NM_000059.4:c.2765dup in the BRCA2 gene and NM_007300.4:c.981_982del and NM_007294.3:c. 5266dup in the BRCA1 gene. p.Lys3326* was the most frequently detected variant of unknown significance (6/ 181). Regarding genotype-phenotype correlations, the NM_007300.4:c.981_982del mutation in BRCA1 gene was found to be milder in terms of breast cancer. The most frequent cancers other than those related to BRCA genes, observed in the relatives of the patients who had pathogenic variants and variants of unknown significance, were endometrium cancer and leukemia, respectively. NM_007294.3:c.5266dup was found to be a candidate founder mutation in the Turkish population. NM_007300.4:c.981_982del mutation seems to have a milder course in terms of breast cancer. A significantly increased frequency of p.Lys3326* variant in breast cancer and ovarian cancer patients compared with that in the 1,000 Genomes Project suggesting that this variant has a slight effect on BRCA2 function.

Appraising the Value of Serum and Serum-Derived Exosomal LncRNA-EXOC7 as a Promising Biomarker in Cervical Cancer

The abnormally expressed long non-coding RNAs (lncRNAs) are closely related to the onset and progression of various malignant tumors. In this study, we aimed to explore the value of serum and serum-derived exosomal lncRNA-EXOC7 (long non-coding RNA exocyst complex component 7) in the diagnosis and monitoring of cervical cancer (CC). The expression of lncRNA-EXOC7 in serum and serum-derived exosomes in CC patients was detected by quantitative real-time PCR (qRT-PCR), and the correlations between lncRNA-EXOC7 expression and clinicopathological characteristics were analyzed by Spearman's and Chi-square tests. Serum vesicles were successfully isolated and identified. The expression of lncRNA-EXOC7 in serum and serum-derived exosomes in CC patients was markedly elevated compared with that in healthy controls. The AUCs of serum and exosomal lncRNA-EXOC7 in distinguishing CC patients from healthy controls were 0.9388 and 0.8982, respectively. The expression of lncRNA-EXOC7 in serum and exosomes was correlated with the FIGO stage of CC (p = 0.041 or 0.010), and positively correlated with levels of CYFRA211, TPS, and SCC (all with p < 0.05). Serum and exosomal lncRNA-EXOC7 was related to the treatment and recurrence of CC; that means, it was significantly repressed after treatment and up-regulated at the time of recurrence. Serum and exosomal lncRNA-EXOC7 can be used as an important biomarker for the diagnosis, the evaluation of curative effect and the detection of recurrence of CC.

Correlation between Pretreatment Hematologic Parameters and Cervical Cancer Patients Undergoing Hysterectomy: a Retrospective Study

The objective of this study is to investigate the correlation of mean platelet volume (MPV), MPV/ platelet count, and monocyte to lymphocyte ratio (MLR) between cervical cancer patients and healthy people and to evaluate the value of those parameters in early diagnosis of cervical cancer. The study population included 137 cervical cancer patients undergoing hysterectomy and 113 healthy controls. The clinical features (age, pathology type, tumor staging, and tumor size) were collected from the hospital information system. The hematology parameters (white blood cell, red blood cell, hemoglobin, platelet count, neutrophil, lymphocyte, monocyte, mean platelet volume, platelet distribution width) are obtained in the laboratory information system. We found that the monocyte count and MLR value are higher in the cervical cancer group. The MPV and MPV/platelet are lower in the cervical cancer group. The receiver operating characteristic (ROC) analysis shows that MPV+MLR can generate a moderate specificity with 71.68%, sensitivity with 65.69%, and AUC with 0.718 to distinguish cervical cancer and healthy people. MPV/platelet and MLR may be helpful for the early diagnosis of cervical cancer. A larger clinical data analysis is necessary to evaluate the diagnostic value of hematologic parameters in cervical cancer.

Application of CircEIF4G2 in Screening of Cervical Lesions

The aim was to investigate the expression of circulating RNA EIF4G2 (CircEIF4G2) in cervical cancer and its correlation with clinicopathological features. Cervical tissue and peripheral blood serum samples were collected from 148 patients with cervical lesions, including 30 patients with low-grade squamous intraepithelial lesions (LSIL group), 35 patients with high squamous intraepithelial lesion (HSIL group), 28 patients with atypical squamous cells (ASC group), and 55 patients with cervical cancer (CC group). At the same time, cervical biopsy specimens and peripheral blood serum were collected from 40 healthy women (Normal group). RT-PCR was used to detect the expression of CircEIF4G2 in cervical tissues and peripheral blood of each group. Electron microscopy was used to observe the distribution of exosomes CircEIF4G2 in cervical tissues. Meanwhile, the correlation between the expression level of CircEIF4G2 and clinical pathological data of patients was analyzed. In vitro, HeLa cells and primary cervical epithelial cells were cultured for 24 hours. Then, the expression levels of CircEIF4G2 in the two kinds of cells were detected by RT-PCR in medium. Furthermore, primary cervical epithelial cells were co-cultured with HeLa cells to observe the effect of exosome CircEIF4G2 on primary cervical epithelial cells. The expression of CircEIF4G2 in the cervical tissue and serum of the normal group was significantly lower than that in the CC group (p < 0.05), but there was no significant difference between the LSIL group and the HSIL group in the cervical tissue and serum (p < 0.05). The distribution and expression of exosomes CircEIF4G2 in each group were consistent with RT-PCR results under an electron microscope. The results of experiments in vitro showed that the expression level of CircEIF4G2 in HeLa cells was significantly higher than that in primary cervical epithelial cells (p < 0.05). The medium in which Hela cells were cultured for 24 hours was added to the culture medium of primary cervical epithelial cells. The process of exosomes CircEIF4G2 entering primary cervical cancer cells was observed by electron microscopy. The increased expression of CircEIF4G2 in tissues and serum of cervical lesions may be caused by the secretion of exosomes containing CircEIF4G2 by cervical cancer cells. Therefore, CircEIF4G2 can be used as a marker for the diagnosis of cervical lesions.

Cervical Cancer Associated Biomarkers of Identify High Risk of Venous Thrombosis

Our study aims to assess the validity of thrombotic biomarkers in estimation of venous thrombosis risk in cervical cancer patients. A total of 134 cervical cancer patients treated in our hospital from September 2016 to November 2017 were selected. Coagulation markers were assayed using Sysmex CA 7000 and HISCL 5000. Baseline demographic and clinical data was then tracked. The levels of plasmin inhibitor-plasmin complex (PIC), thrombin-antithrombin complex (TAT), and D-dimer (DD) were higher in the venous thrombosis positive subgroup, and the increase in levels of PIC, TAT, and DD appears to increase according to their cumulative risk score. Spearman's analysis showed: There was significant positive correlation between the Padua score and the levels of PIC and DD (r = 0.459, 0.488). Generally, studies have confirmed that the levels of PIC and DD may be useful for identifying cervical cancer patients at particularly high risk of thrombosis. Cervical cancer patients who are older, post menopause, receiving surgery or chemotherapy appear to be susceptible to venous thrombosis.

A Study on the Retrospective Reinterpretation of BRCA1 and BRCA2 Variants

Hereditary breast/ovarian cancer is associated with BRCA gene mutations. As large volumes of clinical data on BRCA variants are continuously updated, their clinical interpretation may change, leading to their reclassification. This study analyzed the class and proportion of the changed clinical interpretations of BRCA variants to validate the need for periodic reviews of these variants. This retrospective study reinterpreted previously reported BRCA1 and BRCA2 exon variants according to the 2015 American College of Medical Genetics and Genomics guidelines and the clinical significance of the recent public genomic database. Reanalyzed results were obtained for patients tested for BRCA genetic mutation for 10 years and 4 months. We included data from 4,058 patients, with 595 having at least one pathogenic variant (P), likely pathogenic variant (LP), or variant of uncertain significance (VUS) at a detection rate of 14.66%. The numbers of exon and intron variants were 562 (87.81%) and 78 (12.19%), respectively. BRCA1 exhibited a significantly higher P/LP detection rate of 6.96% compared to that of BRCA2 at 6.89% (p < 0.001). Conversely, BRCA2 demonstrated a significantly higher VUS rate of 10.38% compared to that of BRCA1 at 5.08% (p < 0.001). Among BRCA1 mutations, substitutions were the most prevalent in P/LP and VUS. Among BRCA2 mutations, deletions were most prevalent in P/LP, and substitutions were most prevalent in VUS. Among the 131 patients with P/LP in BRCA1 exons, the clinical interpretation was reclassified in two cases (1.53%), one VUS and one benign/likely benign (B/LB), and 48 cases (48.00%) with VUS were reclassified; one to P/LP and 47 to B/LB. Among the 138 patients with P/LP in BRCA2 exons, the clinical interpretation was reclassified in six (4.35%), five to VUS, and one to B/LB, and all 74 with VUS were reclassified to B/LB. We determined the class and proportion of reclassified BRCA variants. In conclusion, reviews are required to provide clinical guidance, such as determining treatment direction and preventive measures in the future.

Immunohistochemical Profiles of p53 and ER in Relation to Lesion Type, Tumor Grade, and Pathological Features in Endometrial Cancer

The goal was to assess the pathological measurements of estrogen receptor (ER) and p53 expression in tissues of uterine endometrial carcinoma and their relationship to various clinicopathologic parameters that influence prognosis. The current study included 40 cases of endometrial carcinoma in total hysterectomy samples obtained from the preservation documents of the Al Azhar University Hospitals along with certain privately operated laboratories between April 2023 and April 2025. Each of the samples was formalin-fixed, subsequently processed and placed inside paraffin blocks. Several serial 5-micron thick sections were extracted from the samples' paraffin blocks; one was stained with hematoxylin and eosin for histopathological analysis to figure out tumor histology, grade, and lymphovascular invasion, whereas the remaining sections were put on positively charged slides and im-munostained with mouse monoclonal antibodies against p53, as well as rabbit monoclonal antibodies against ER. The mean age of the study group was 52.20 ± 12.25 years ranging from 38 - 69; 25 (62.5%) had type I lesions and 15 (37.5%) had type II lesions. Twenty-six (65.0%) had wild (normal) IHC: p53 and 14 (35.0%) had mutant (abnormal) IHC: p53. Eleven (27.5%) were negative for IHC: ER and 29 (72.5%) were positive for IHC: ER. There was highly statistically significant association between IHC: p53 and type of lesions (p = 0.001) and statistically significant association between IHC: p53 and grade of pathology (p = 0.007). There were highly statistically significant associations between IHC: ER and lesions (p = 0.001), lymphovascular invasion (p = 0.001) and statistically significant association between IHC: ER and grade of pathology (p = 0.013). There was statistically significant association between IHC: p53 and IHC: ER (p = 0.014). p53 and ER markers were discovered to have a pathological significance in EC. There is a link among these markers and other clinicopathological predictive measures, suggesting that they could serve as possibly beneficial biomarkers.

Correlation between Lipoprotein(a) and Endometrial Cancer Prognosis: a Retrospective Cohort Study

Endometrial cancer (EC) is a malignant tumor arising from the endometrial epithelium and is among the most prevalent gynecological malignancies worldwide. Increasing evidence suggests that lipid profiles, hyperglycemia, and other metabolic factors play a role in EC pathogenesis. However, research on the association between lipoprotein(a) [Lp(a)] levels and EC prognosis remains limited. This retrospective cohort study analyzed Lp(a) levels in patients diagnosed with EC at Ganzhou Hospital, affiliated with Nanchang University, between January 2017 and January 2022. Lp(a) concentrations were measured post-admission, and patient prognosis was categorized as favorable or poor. Multivariate logistic regression analysis was performed to determine the adjusted odds ratio (OR) and 95% confidence interval (CI). The study included 296 EC patients, out of whom 72.3% (214/296) had a favorable prognosis, defined as no recurrence within five years post-surgery. The overall healing rate was 72.3% (214/296). When stratified by Lp(a) levels, patients in the first quantile (Q1 ≤ 122.2 g/L) had a favorable prognosis rate of 77.7% (115/148), whereas those in the second quantile (Q2 > 122.2 g/L) had a rate of 66.9% (99/148), with a statistically significant difference between groups (p < 0.05). In the multivariate regression model, the log2-transformed Lp(a) values and their corresponding ORs (95% CIs) for prognosis at two upper normal limits (ULN) were 1.7248 (1.0288 - 2.8918) and 2.0365 (1.1843 - 3.5018), respectively. Interaction analysis indicated that Lp(a) levels significantly influenced EC prognosis. Lp(a) is strongly associated with EC prognosis and holds potential clinical significance. Further studies are required to validate these findings.

Tislelizumab Combined with Carboplatin-Paclitaxel for Treatment of Metastatic or Recurrent Endometrial Cancer: a Retrospective Clinical Study

Metastatic or recurrent endometrial cancers with low survival rate had no standard or limited therapy choice. The aim of our study was to determine the efficiency and safety of tislelizumab combined with carboplatin-paclitaxel as a front-line therapy for patients with metastatic or recurrent endometrial cancer. This clinical retrospective cohort study examined 24 Chinese patients with metastasis or recurrence but had not yet received treatment. The therapeutic regimen consisted of 6 cycles of intravenous paclitaxel (175 mg/m2) and carboplatin (target AUC: 5 mg/mL/min) with tislelizumab (200 mg) once every 3 weeks, and then intravenous tislelizumab (200 mg) once every 3 weeks until disease progression or unacceptable toxicity. At the 18-month follow-up, 8 patients were still receiving treatment, 13 were dead, and 3 withdrew. The objective response rate (ORR) was 62.5%, the disease control rate was 75.00%. The ORR was 77.78% for patients positive for PD-L1 and 69.23% for patients positive for MSI-H. The median overall survival time was 11.50 months, and the median progression-free survival time was 6.00 months. Half of the patients experienced 3 - 4 grade adverse events. There were no allergic reactions or treatment-related deaths. Tislelizumab combined with carboplatin-paclitaxel was used as a front-line therapy, had a beneficial effect and was safe for patients with metastatic or recurrent endometrial cancer.

Identification of an Immune-Related LncRNA Prognostic Signature in Uterine Corpus Endometrial Carcinoma Patients

Uterine corpus endometrial carcinoma (UCEC) is the third most prevalent female reproductive system malignant tumor with poor prognosis, particularly at advanced stage. On the other hand, recent studies have reported the prognostic role of long non-coding RNAs (lncRNAs) in UCEC. The aim of this study was to determine the immune-related lncRNA signature for predicting overall survival (OS) in UCEC patients. The genomic data and clinical information of UCEC patients were extracted from the Cancer Genome Atlas. Pearson's correlation analysis was carried out to identify the immune-related lncRNAs. Univariate and multivariate Cox regression analyses were conducted to obtain the prognostic lncRNAs from the immune-related lncRNAs for the construction of the prognostic signature. Afterwards, the UCEC patients were divided into high-risk and low-risk groups. The prognostic value of the signature was assessed by survival, receiver operating characteristic (ROC), and nomogram analyses. Finally, the immune status for high-risk and low-risk groups was evaluated by the ESTIMATE algorithm. A total of 13 immune-related lncRNAs (AC108860.2, AC015849.5, AL592494.3, LINC01234, U91319.1, AC092969.1, AL356133.2, AC103563.2, AL138962.1, AC138965.1, LINC01687, AC091987.1, and MIR7-3HG) were finally identified for the construction of the prognostic signature. Patients in the high-risk group had worse prognosis than those in the low-risk group. The prognostic signature was confirmed as an independent prognostic factor through the multivariate Cox regression analysis. The nomogram based on the prognostic signature and clinicopathologic features was constructed with a superior overall predictive power to evaluate the survival outcomes in UCEC patients. Finally, according to the ESTIMATE algorithm results, we discovered different immune statuses in the low-risk and high-risk groups. The immune-related lncRNA signature for the assessment of the OS of UCEC patients had a good practical value.