Journal

Journal of Obstetrics and Gynaecology

Papers (209)

The bioinfomatics analysis of the M1 macrophage-related gene CXCL9 signature in cervical cancer

The expression and function of coexpression genes of M1 macrophage in cervical cancer have not been identified. And the CXCL9-expressing tumour-associated macrophage has been poorly reported in cervical cancer. To clarify the regulatory gene network of M1 macrophage in cervical cancer, we downloaded gene expression profiles of cervical cancer patients in TCGA database to identify M1 macrophage coexpression genes. Then we constructed the protein-protein interaction networks by STRING database and performed functional enrichment analysis to investigate the biological effects of the coexpression genes. Next, we used multiple bioinformatics databases and experiments to overall investigate coexpression gene CXCL9, including western blot assay and immunohistochemistry assay, GeneMANIA, Kaplan-Meier Plotter, Xenashiny, TISCH2, ACLBI, HPA, TISIDB, GSCA and cBioPortal databases. There were 77 positive coexpression genes and 5 negative coexpression genes in M1 macrophage. The coexpression genes in M1 macrophage participated in the production and function of chemokines and chemokine receptors. Especially, CXCL9 was positively correlated with M1 macrophage infiltration levels in cervical cancer. CXCL9 expression would significantly decrease and high CXCL9 levels were linked to good prognosis in the cervical cancer tumour patients, it manifestly expressed in blood immune cells, and was positively related to immune checkpoints. CXCL9 amplification was the most common type of mutation. The CXCL9 gene interaction network could regulate immune-related signalling pathways, and CXCL9 amplification was the most common mutation type in cervical cancer. Meanwhile, CXCL9 may had clinical significance for the drug response in cervical cancer, possibly mediating resistance to chemotherapy and targeted drug therapy. Our findings may provide new insight into the M1 macrophage coexpression gene network and molecular mechanisms in cervical cancer, and indicated that M1 macrophage association gene CXCL9 may serve as a good prognostic gene and a potential therapeutic target for cervical cancer therapies.

A retrospective study of Pipelle endometrial biopsy for ovarian, fallopian tube, and peritoneal cancers

Although the Pipelle endometrial biopsy is widely performed as a practical and minimally invasive test for endometrial disease(s), its effectiveness in ovarian cancer has not been explored. The aim of the present study was to evaluate the results of Pipelle endometrial biopsy for ovarian, fallopian tube, and peritoneal cancers. A pre-treatment Pipelle-endometrial biopsy was performed in 90 patients with ovarian, fallopian tube, or peritoneal cancers between January 2014 and November 2021. We retrospectively analysed the association between the results of Pipelle endometrial biopsy and clinicopathological data. Moreover, we evaluated their impact on the following treatment in advanced cases initially treated with chemotherapy. The sensitivity and false-negative rates for Pipelle endometrial biopsy were 25/90 (27.8%) and 65/90 (72.2%) in all patients, respectively, and 23/56 (41.0%) and 33/56 (58.9%) in cases with advanced disease (stages III and IV), respectively. Pipelle-positive endometrial biopsy-positive (Pipelle-positive) was not observed in 29 patients with clinical stage I disease, and Pipelle-positive patients exhibited significantly more high-grade serous carcinomas, and positive peritoneal, endometrial, and cervical cytologies than Pipelle-endometrial biopsy-negative cases. Surgical pathology was confirmed in 23 Pipelle-positive patients, and 17/23 (74.0%) had the same diagnosis as that for Pipelle endometrial biopsy. Conversely, 6/23 (26.0%) patients exhibited a minor diagnostic discrepancy between Pipelle endometrial biopsy and surgical pathology. Nineteen of the 38 (50.0%) patients initially treated with chemotherapy were identified as Pipelle-positive, contributing to a prompt histological diagnosis and pre-treatment tumour sampling. Companion diagnostic tests were performed using Pipelle endometrial biopsy samples from 4 inoperable patients. Although the positive rate of Pipelle endometrial biopsy in ovarian, fallopian tube, and peritoneal cancers is low, Pipelle endometrial biopsy may enable prompt histological diagnosis and initiation of chemotherapy while collecting tumour tissue for genetic testing in some cases with advanced disease.

Retrospective analysis of metabolism-related genes in endometrial carcinoma: links to prognosis and immunity

Endometrial carcinoma is a clinically complex gynaecologic malignancy exhibiting significant molecular heterogeneity. This heterogeneity manifests as marked variability in clinical outcomes and heterogeneous therapeutic responses to emerging treatment modalities, particularly to immune checkpoint inhibitors. Metabolic reprogramming has been implicated in tumour progression and immune evasion in endometrial carcinoma. However, the prognostic implications of metabolism-related genes and their interaction with the tumour immune microenvironment remain insufficiently characterised. RNA-seq and clinical data of endometrial carcinoma were downloaded from The Cancer Genome Atlas (TCGA) database, along with a metabolism-related gene set (MRGs) curated from the Msigdb database. Differential expression analysis was conducted to identify differentially expressed metabolism-related genes (DE-MRGs), which were subsequently analysed to evaluate their expression patterns and prognostic significance in uterine corpus endometrial carcinoma. Functional enrichment was performed via GO and KEGG analysis. The CIBEROSRT computational algorithm was employed to quantify immune infiltration characteristics and their correlation with MRGs. Furthermore, an external GEO dataset (GSE17025) was employed to validate hub gene expression. A total of 49 differentially expressed MRGs were identified in endometrial carcinoma. Functional analyses showed enrichment in retinol and tyrosine metabolism pathways. Two hub genes, LIPG and DDC, were significantly associated with overall survival ( Our study analysed the expression and prognostic relevance of MRGs of endometrial carcinoma. We validated the prognostic value of MRGs and their potential to offer novel insights into prognostication and personalised treatment strategies for endometrial carcinoma.

CircRNA circ_0005273 contributes to the cisplatin resistance of cervical cancer cells by sponging miR-133b

Circular RNAs (circRNAs) have been found to play important roles in drug resistance of human neoplasms. The aim of this study was to explore the effect of circ_0005273 on cisplatin (DDP) resistance of cervical cancer (CC) cells and identify its underlying mechanism. The quantitative real-time polymerase chain reaction (qRT-PCR) was performed to analyse circ_0005273 and miR-133b expressions, and cell counting kit-8 (CCK-8), Hoechst 33258 staining and caspase-3 activity analysis were performed to evaluate cell proliferation and apoptosis. Luciferase reporter, RNA binding protein immunoprecipitation (RIP) and RNA pull down assays were applied to explore the interaction between circ_0005273 and miR-133b. Our research showed that circ_0005273 and miR-133b expressions were upregulated and downregulated in DDP-resistant CC cancer tissues and cell lines, respectively. Both of circ_0005273 and miR-133b levels were correlated with FIGO stage, DDP status and overall survival rates. Knockdown of circ_0005273 enhanced the sensitivity of DDP-resistant CC cells to DDP by inhibiting cell proliferation and promoting cell apoptosis. Furthermore, circ_0005273 acts as a competing endogenous RNA to modulate miR-133b expression. Downregulation of miR-133b partly reversed the DDP sensitivity of circ_0005273 knockdown in DDP-resistant CC cells. In summary, our study elucidated the role of circ_0005273/miR-133b axis in DDP resistance of CC cells, which might be a potential therapeutic target for DDP-resistant CC patients. Impact Statement

Outcomes of transvaginal natural orifice transluminal endoscopic hysterectomy: a multi-centre retrospective study from Turkey (TR-MIGS)

Vaginal natural orifice transluminal endoscopic surgery (vNOTES) hysterectomy is gaining increasing popularity among gynaecological surgeons worldwide due to its minimally invasive nature and associated benefits. However, despite its growing adoption, it remains a relatively novel surgical technique that continues to be evaluated and refined in clinical practice. The primary objective of this study is to share and analyse our initial experiences with the implementation of vNOTES hysterectomy across six specialised gynaecological centres in Turkey. This retrospective analysis included all women who underwent vNOTES hysterectomy, with or without salpingo-oophorectomy, for benign or malignant conditions. All procedures adhered to the standardised protocol described by Baekelandt A total of 685 patients underwent vNOTES procedures. Among them, 64 women (9.3%) had a history of one caesarean delivery, 38 (5.5%) had two prior caesareans, and 11 (1.6%) had three or more. Myoma, with or without accompanying metrorrhagia, was the most common surgical indication (53.0%). The mean operative time was 72.4 ± 40.2 min, and the average haemoglobin decrease was 1.3 ± 1.0 g/dL. The mean uterine weight was 204 ± 145 g. Intraoperative complications occurred in 1.7% of cases ( These findings support vNOTES as a safe and effective surgical approach, offering a viable alternative to traditional laparoscopic or vaginal techniques in select patient populations.

CST2 promotes cell proliferation and regulates cell cycle by activating Wnt-β-catenin signalling pathway in serous ovarian cancer

Cystatin SA (CST2) plays multiple roles in different types of malignant tumours; however, its role in serous ovarian cancer (SOC) remains unclear. Therefore, we aimed to investigate the expression levels, survival outcomes, immune cell infiltration, proliferation, cell cycle, and underlying molecular mechanisms associated with the CST2 signature in SOC. The Cancer Genome Atlas database was used to acquire clinical information and CST2 expression profiles from patients with SOC. Wilcoxon rank-sum tests were used to compare CST2 expression levels between SOC and normal ovarian tissues. A prognostic assessment of CST2 was conducted using Cox regression analysis and the Kaplan-Meier method. Differentially expressed genes were identified using functional enrichment analysis. Immune cell infiltration was examined using a single-sample gene set enrichment analysis. Cell cycle characteristics and proliferation were assessed using a colony formation assay, flow cytometry, and a cell counting kit-8 assay. Western blots and quantitative reverse transcription PCR analyses were employed to examine CST2 expressions and related genes involved in the cell cycle and the Wnt-β-catenin signalling pathway. Our findings revealed significant upregulation of CST2 in SOC, and elevated CST2 expression was correlated with advanced clinicopathological characteristics and unfavourable prognoses. Pathway enrichment analysis highlighted the association between the cell cycle and the Wnt signalling pathway. Moreover, increased CST2 levels were positively correlated with immune cell infiltration. Functionally, CST2 played vital roles in promoting cell proliferation, orchestrating the G1-to-S phase transition, and driving malignant SOC progression through activating the Wnt-β-catenin signalling pathway. The elevated expression of CST2 may be related to the occurrence and progression of SOC by activating the Wnt-β-catenin pathway. Additionally, our findings suggest that CST2 is a promising novel biomarker with potential applications in therapeutic, prognostic, and diagnostic strategies for SOC.

Outcomes of minimal access retroperitoneal para-aortic lymphadenectomy in patients with locally advanced cervical cancer

To evaluate outcomes of laparoscopic retroperitoneal para-aortic lymphadenectomy for stage 1b3-3b cervical cancer. Pathology databases searched for all para-aortic lymphadenectomy cases 2005-2016. Descriptive statistics were used to analyse baseline characteristics, cox models for treatment affect after accounting for variables, and Kaplan Meier curves for survival (STATA v15). 191 patients had 1b3-3b cervical cancer of which 110 patients had Para-aortic lymphadenectomy. 8 (7.3%) patients stage 1b3, 82 (74.6%) stage 2b, and 20 (18.1%) stage 3b cervical cancer. Mean lymph node count 11.7 (SD7.6). The intra-operative and post-operative 30 day complication rates were 8.8% (CI: 4.3%, 15.7%) and 5.3% (CI: 1.9%, 11.2%) respectively.Para-aortic nodes were apparently positive on CT/MRI in 5/110 (5%) cases. Cancer was found in 10 (8.9%, CI: 4.3%, 15.7%) cases on histology, all received extended field radiotherapy. Only 2 were identified on pre-operative CT/MRI imaging. 3 of 10 suspected node-positive cases on CT/MRI had negative histology. Para-aortic lymphadenectomy led to alteration in staging and radiotherapy management in 8 (8%, CI: 3.7%, 14.6%) patients. Mean overall survival 42.81 months (SD = 31.79 months). Survival was significantly higher for women undergoing PAN (50.57 (SD 30.7) months) compared to those who didn't (31.27 (SD 32.5) months). Laparoscopic retroperitoneal para-aortic lymphadenectomy is an acceptable procedure which can guide treatment in women with locally advanced cervical cancer.

The oncogenic roles of GPR176 in ovarian cancer: a molecular target for aggressiveness and gene therapy

At present, the discovery of new biomarkers is of great significance for the early diagnosis, treatment and prognosis assessment of ovarian cancer. Previous findings indicated that aberrant G-protein-coupled receptor 176 (GPR176) expression might contribute to tumorigenesis and subsequent progression. However, the expression of GPR176 and the molecular mechanisms in ovarian cancer had not been investigated. GPR176 expression was compared with clinicopathological features of ovarian cancer using immunohistochemical and bioinformatics analyses. GPR176-related genes and pathways were analysed using bioinformatics analysis. Additionally, the effects of GPR176 on ovarian cancer cell phenotypes were investigated. GPR176 expression positively correlated with elder age, clinicopathological staging, tumour residual status, and unfavourable survival of ovarian cancer, but negatively with purity loss, infiltration of B cells, and CD8+ T cells. Gene Set Enrichment Analysis showed that differential expression of GPR176 was involved in focal adhesion, ECM-receptor interaction, cell adhesion molecules and so on. STRING and Cytoscape were used to determine the top 10 nodes. Kyoto Encyclopaedia of Genes and Genomes analysis indicated that GPR176-related genes were involved in the ECM structural constituent and organisation and so on. GPR176 overexpression promoted the proliferation, anti-apoptosis, anti-pyroptosis, migration and invasion of ovarian cancer cells with overexpression of N-cadherin, Zeb1, Snail, Twist1, and under-expression of gasdermin D, caspase 1, and E-cadherin. GPR176 might be involved in the progression of ovarian cancer. It might be used as a biomarker to indicate the aggressive behaviour and poor prognosis of ovarian cancer and a target of genetic therapy.

Human papillomavirus: present and future perspective in Saudi Arabia

Human papillomavirus (HPV) is a widely dispersed DNA double-stranded carcinogenic virus worldwide. Many cancers have been attributed to HPV subtypes as a major aetiological factor. Around 90% of cervical cancers have been attributed to the HPV infection, in addition to other cancers such as head and neck cancer, breast cancer and other cancers. As the carcinogenic high risk and low-risk, HPV subtypes are sexually transmitted viruses, and the Saudi community is religiously conservative, lots of measures of the precise burden of the HPV and its related cancers are still obscure. With the absence of cervical-screening programmes and in-depth research in HPV-related cancers, there a lack of literature except for literature pertained to awareness and perceptions. Consequently, the present review is deemed to explore the present state of the HPV-related issues, the future perspective in light of the current scientific evidence, as well as, Saudi community practices, and health policies in this regard. Making accessible data on HPV-related cancers can assist in designing HPV-related early detection and control sustainable programmes. Therefore, this review aimed to discuss the most important magnitudes related to the HPV, concerning the available literature from Saudi Arabia and the data in the neighbouring Arab countries interrelated to Saudi Arabia. The review depended on searching Electronic databases using strongly considered indexes including PubMed, Medline, Web of Science, Scopus, ABSCO, EMBASE, and others. In conclusion, though Saudi Arabia is pronounced as a conservative community with low sexual transmitted diseases, there is an alarming menace of HPV-attributable diseases necessitating a quick intervention.

Postoperative nomogram for the prediction of disease-free survival in lymph node-negative stage I–IIA cervical cancer patients treated with radical hysterectomy

The purpose of this study was to develop and validate a nomogram for individual prediction of recurrence and disease-free survival (DFS) among lymph node (LN)-negative early-stage (I-IIA) cervical cancer (CC) patients treated with Type B or Type C2 hysterectomy. Data were collected from patients diagnosed with CC between 1995 and 2017 at the Gynecological Oncology Department, Tepecik Training and Research Hospital. A total of 194 cases with stage IA2-IIA CC were evaluated retrospectively. Patients with stage IA2-IIA CC who underwent radical (Type C2) or modified radical (Type B) hysterectomy and pelvic ± paraaortic LN dissection with LN negativity were included in the study. The relationships between prognostic factors such as stage, tumour size, parametrial involvement, vaginal cuff margin, endomyometrial infiltration, and lymphovascular space invasion status and DFS were compared using a univariable Cox regression model. When the nomogram was prepared, the scores of the risk factors were collected, and we observed that scores were at least 0 to a maximum of 414 points. The concordance-index for the nomogram was 0.895 (95% confidence interval, 0.79-0.99). The nomogram based on the indicated prognostic factors yielded excellent results in predicting recurrence in early-stage CC patients without LN metastasis who underwent radical hysterectomy.Impact statement

Outcomes of laparoscopic myomectomy for large and high-order fibroids: a single-centre service evaluation

Ethnic minority patients experience a higher uterine fibroid disease burden and reduced access to minimally invasive myomectomy. Restrictive selection criteria may disproportionately exclude these patients from laparoscopic surgery. This was a prospective service-evaluation database analysed retrospectively, including all conventional (non-robotic) laparoscopic myomectomies performed between January 2004 and December 2024 at a single UK university hospital. Primary outcomes were estimated blood loss (EBL), length of hospital stay (LOS) and operating time. Secondary outcomes were blood transfusion rate, conversion to laparotomy and analysis of fibroid burden by ethnicity. Outcomes were compared between patients with large fibroids (>10 cm), high-order fibroids (>10 fibroids removed), both and neither. We performed inferential descriptive statistics using SPSS v27 (SPSS Inc., Chicago, IL). Among 550 patients, 164 had large fibroids, 30 high-order fibroids, 18 both and 338 neither. Ethnic minority patients represented 77%, 93%, 89% and 72% of these groups, respectively. Mean EBL was higher in large fibroid (345 mL) and combined groups (483 mL) compared with neither (211 mL), without associated increases in transfusion, conversion to laparotomy, or LOS. Black African and Black Caribbean patients had greater fibroid burden and higher blood loss than Caucasian patients, reflecting disease severity rather than ethnicity as an independent determinant of outcome. In a specialist setting, laparoscopic myomectomy is feasible and safe for patients with large and/or multiple fibroids, including those from ethnic minority backgrounds with higher disease burden. Expansion of access within appropriately resourced centres may help reduce inequities in fibroid care.

Multi-institutional validation of the ESMO-ESGO-ESTRO consensus conference risk grouping in Turkish endometrial cancer patients treated with comprehensive surgical staging

In this study, 683 patients with endometrial cancer (EC) after comprehensive surgical staging were classified into four risk groups as low (LR), intermediate (IR), high-intermediate (HIR) and high-risk (HR), according to the recent consensus risk grouping. Patients with disease confined to the uterus, ≥50% myometrial invasion (MI) and/or grade 3 histology were treated with vaginal brachytherapy (VBT). Patients with stage II disease, positive/close surgical margins or extra-uterine extension were treated with external beam radiotherapy (EBRT)±VBT. The median follow-up was 56 months. The overall survival (OS) was significantly different between LR and HR groups, and there was a trend between LR and HIR groups. Relapse-free survival (RFS) was significantly different between LR and HIR, LR and HR and IR and HR groups. There was no significant difference in OS and RFS rates between the HIR and HR groups. In HR patients, the OS and RFS rates were significantly higher in stage IB - grade 3 and stage II compared to stage III and non-endometrioid histology without any difference between the two uterine-confined stages and between stage III and non-endometrioid histology. The current risk grouping does not clearly discriminate the HIR and IR groups. In patients with comprehensive surgical staging, a further risk grouping is needed to distinguish the real HR group.Impact statement

Integrated bioinformatic and experimental study links cyclin B1/B2 to poor prognosis and immune infiltration in endometrial cancer

Although most cases of endometrial cancer (EC) are diagnosed at an early stage with favourable outcomes, the prognosis for advanced or recurrent disease remains poor, highlighting the need for novel therapeutic targets. This study aimed to examine the correlation between Cyclin B1 (CCNB1) and Cyclin B2 (CCNB2) expression and disease severity in EC through bioinformatics analysis. Common differentially expressed genes were identified in two EC cohorts from the Gene Expression Omnibus. A protein-protein interaction (PPI) network was constructed to identify hub genes. Aberrant expression of the hub genes was validated in external datasets. Their prognostic values were evaluated in a cohort from The Cancer Genome Atlas (TCGA). Knockdown of the hub genes was conducted to explore their functions in the malignant behaviour of EC cells CCNB1 and CCNB2 were identified as the top 2 hub genes in the PPI network. High CCNB1/CCNB2 expression was significantly associated with shorter survival in EC patients. Overexpression of CCNB1/CCNB2 in endometrial tumour tissue was validated in public datasets. In TCGA cohort, high expression of CCNB1/CCNB2 correlated with greater disease severity and predicted poor prognosis. In addition, high expression of CCNB1/CCNB2 was strongly associated with immune cell infiltration, as well as increased expression of immune checkpoint genes and mismatch repair genes. Furthermore, knockdown of CCNB1/CCNB2 significantly suppressed the proliferation, migration, and invasion of HEC-1 and Ishikawa cells CCNB1 and CCNB2 may serve as potential prognostic markers and therapeutic targets for the management of EC.

The differential expression of AFF3 in cervical cancer and its correlation with clinicopathological features and prognosis

Cervical cancer (CC) is the second most common malignancy in women, and identifying biomarkers of CC is crucial for prognosis prediction. Here, we investigated the expression of AF4/FMR2 Family Member 3 (AFF3) in CC and its association with clinicopathological features and prognosis. Tumour and adjacent tissues, along with clinicopathological features and follow-up information, were collected from 78 patients. AFF3 expression was assessed using quantitative real-time polymerase chain reaction and Western blotting. The correlation between AFF3 expression and CC symptoms was using chi-square test. The 5-year overall survival (OS) was analysed using the Kaplan-Meier method. The Univariate analysis of prognostic risk factors was conducted using the COX proportional hazards model, followed by multivariate COX regression analysis including variables with AFF3 expression was downregulated in CC, and its levels were correlated with lymph node metastasis (LNM) and International Federation of Gynaecology and Obstetrics (FIGO) stage. Patients with low AFF3 expression had a lower 5-year OS rate (52.78%, 19/36). Postoperative survival was reduced in patients with histological grade 3 (G3), myometrial invasion (depth ≥ 1/2), lymphovascular space invasion, LNM, and advanced FIGO stage. Low expression of AFF3 (HR: 2.848, 95% CI: 1.144-7.090) and histological grade G3 (HR: 4.393, 95% CI: 1.663-11.607) were identified as independent prognostic risk factors in CC patients. Low expression of AFF3 and histological G3 are independent predictors of poor prognosis in CC patients, suggesting that AFF3 could serve as a potential biomarker for prognostic assessment in CC.

LINC01094 targets miR-1266-5p to halt neoplasm progression of cervical cancer

To investigate the mechanism and prognostic value of LINC01094 in cervical cancer (CC). This study included 113 patients with CC. Their cervical tumour tissues and tumour-free cervical tissues were collected, with patient follow-up for a five-year prognostic period. Reverse transcription-quantitative PCR (RT-qPCR) was used to identify LINC01094 and measure miR-1266-5p expression, Kaplan-Meier curves were used to predict patient survival, and multivariate Cox regression analysis revealed the factors affecting CC prognosis. A dual luciferase reporter (DLR) assay was performed to verify the targeting relationship of reciprocal genes. The Cell Counting Kit-8 (CCK8) assay was used to measure cell proliferation, and the Transwell recorded cell migration and invasion. Lower LINC01094 expression and higher level of miR-1266-5p expression were detected in-tumour tissues than in the tumour-free cervical tissues, with a negative correlation. Low LINC01094 expression, International Federation of Gynaecology and Obstetrics (FIGO) stage, and lymph node metastasis were identified as risk factors for CC prognosis, LINC01094 downregulation predicted higher patient mortality. The DLR assay identified miR-1266-5p as a possible target gene of LINC01094. Additional experiments revealed miR-1266-5p downregulation and decreased cell proliferation, migration and invasion of CC cells transfected with oe-LINC01094. These effects were restored after co-transfection with miR-mimic. Low LINC01094 expression in patient with CC is a risk factor for prognosis. Overexpression of LINC01094 targeting miR-1266-5p prevents the progression of CC neoplasm.

Demographics of epithelioid trophoblastic tumour and placental site trophoblastic tumour: a 21 year UK population study

Epithelioid and placental site trophoblastic tumours are rare gestational malignancies which have little detailed information on their population incidence or risk related to maternal age. We performed a retrospective UK national population-based study examining all of the cases registered between 2000 and 2020 using the databases at the UK's two gestational trophoblastic treatment centres at Charing Cross Hospital in London and Weston Park Hospital in Sheffield. The data obtained was compared with the contemporary UK birth and pregnancy statistics. Over the 21-year study period, there were 132 cases of ETT or PSST. PSTT comprised 57% of the cases, 30% were ETT and 13% had mixed pathology. The combined incidence of ETT and PSTT was 1:118,736 relative to live births and 1:150,872 compared to total viable conceptions. For women aged under 20 the incidence relative to live births was 1:412,488, increasing to 1:188,292 for women 30-34 years, and 1:1,426 for women aged 45 and above. The median interval from the antecedent pregnancy to the time of diagnosis was 15 months (0-288) for the PSTT patients compared to 24 months (0-336) for patients with a diagnosis of ETT. ETT and PSTT are both rare diagnoses with little detailed information on their demographics. The data in this study indicates a wide range in the interval from the antecedent pregnancy to diagnosis and confirms a close relationship between increasing incidence and rising maternal age.

Meta-analysis of efficacy and safety of pembrolizumab for the treatment of advanced or recurrent cervical cancer

This meta-analysis seeks to assess the efficacy and safety of pembrolizumab in individuals with advanced or recurrent cervical cancer. Databases from PubMed, Embase, and the Cochrane Library were all thoroughly searched for pertinent research. Outcomes include complete response (CR), partial response (PR), stable disease (SD), disease progression (PD), overall response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (mOS), and adverse events (AEs) were retrieved for further analysis. Ten trials with 721 patients were included in this meta-analysis. The pooled results for patients with cervical cancer receiving pembrolizumab were as follows: CR (0.06, 95%CI: 0.02-0.10), PR (0.15, 95%CI: 0.08-0.22), SD (0.16, 95%CI: 0.13-0.20), PD (0.50, 95%CI: 0.25-0.75), ORR (0.26, 95%CI: 0.11-0.41) and DCR (0.42, 95%CI: 0.13-0.71), respectively. Regarding survival analysis, the pooled mPFS and mOS were 3.81 and 10.15 months. Subgroup analysis showed that pembrolizumab in combination was more beneficial in CR (0.16 vs. 0.03, For patients with advanced or recurrent cervical cancer, this systematic review and meta-analysis demonstrated that pembrolizumab had a favourable efficacy and tolerability. Future research will primarily focus on optimising customised regiments that optimally integrate pembrolizumab into new therapies and combination strategies. Designed to maximise patient benefit and efficiently control adverse effects while maintaining a high standard of living.

Prediction of outcomes after chemoradiotherapy for cervical cancer by neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio

Cervical cancer ranks as the second most fatal tumour globally among females. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been widely applied to the diagnosis of cancers. The clinicopathologic data of 180 patients with stage IB2-IIB cervical cancer who underwent radical concurrent chemoradiotherapy from January 2018 to December 2019 were retrospectively analysed. Receiver operating characteristic (ROC) curves were plotted to analyse the optimal cut-off values of NLR and PLR for predicting the therapeutic effects of concurrent chemoradiotherapy. The associations of PLR and other clinicopathological factors with 1-year survival rates were explored through univariate analysis and multivariate Cox regression analysis, respectively. NLR was significantly associated with the therapeutic effects of neoadjuvant therapy, with the optimal cut-off value of 2.89, area under the ROC curve (AUC) of 0.848 (95% confidence interval [CI]: 0.712-0.896), sensitivity of 0.892 (95% CI: 0.856-0.923) and specificity of 0.564 (95% CI: 0.512-0.592). PLR had a significant association with the therapeutic effects of neoadjuvant therapy, with the optimal cut-off value of 134.27, AUC of 0.766 (95% CI: 0.724-0.861), sensitivity of 0.874 (95% CI: 0.843-0.905) and specificity of 0.534 (95% CI: 0.512-0.556). Lymphatic metastasis ([95% CI: 1.435-5.461], [95% CI: 1.336-4.281], depth of invasion ([95% CI: 1.281-3.546], [95% CI: 1.183-3.359]) and tumour size ([95% CI: 1.129-3.451], [95% CI: 1.129-3.451]) were independent factors influencing the overall survival and disease-free survival (DFS) of patients with cervical cancer. NLR (95%CI: 1.256-4.039) and PLR (95%CI:1.281-3.546) were also independent factors affecting DFS. NLR and PLR in the peripheral blood before treatment may predict DFS of patients with stage IB2-IIB cervical cancer.

Efficacy and safety of intraperitoneal bevacizumab combined with hyperthermic intraperitoneal chemotherapy in the treatment of patients with ovarian cancer and peritoneal effusion and the effect on serum lncRNA H19 and VEGF levels

Peritoneal effusion is a common event in ovarian cancer (OC) patients. LncRNA H19 and vascular endothelial growth factor (VEGF) are implicated in cancer progression. The study evaluated the curative effect and safety of bevacizumab combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in OC patients with peritoneal effusion and the effect on serum lncRNA H19/VEGF levels. Totally 248 OC patients with peritoneal effusion were treated with intraperitoneal bevacizumab + HIPEC (observation group) or abdominal paracentesis without HIPEC (control group). The clinical efficacy, quality of life, and adverse reactions were evaluated after two treatment cycles. The serum lncRNA H19 and VEGF levels pre-/post-treatment were determined by RT-qPCR and ELISA. The observation group exhibited better clinical efficacy than the control group, evidenced by a higher partial response rate, response rate, and disease control rate. The observation group exhibited reduced physical/cognitive/role/social/emotional function scores and total adverse reactions. LncRNA H19/VEGF levels showed no significant difference between the two groups before treatment but were significantly downregulated in the observation group after treatment. Summarily, intraperitoneal bevacizumab + HIPEC has significant efficacy in treating peritoneal effusion, improves the quality of life, and reduces serum lncRNA H19 and VEGF levels in OC patients, with fewer adverse reactions and higher safety.Impact statement

Effect of lncRNA LINC00324 on cervical cancer progression through down-regulation of miR-195-5p

Long non-coding RNAs (lncRNAs) have been widely used in the exploration of diseases in recent years. This paper introduced the significance of lncRNA LINC00324 (LINC00324) on the progression of cervical cancer and explored the mechanism of action and potential prognosis of LINC00324. The cervical cancer tissues and adjacent normal tissues of 120 people were collected as research samples. The expression level of LINC00324 was assessed by RT-qPCR, as was miR-195-5p. Knockdown of LINC00324 on the proliferation ability of cervical cancer cells was determined with the help of cell counting kit-8 (CCK-8), and the number of cell migration and invasion was detected by the Transwell method. Luciferase reporter gene assay was used to analyse the correlation of LINC00324 and miR-195-5p. Kaplan-Meier survival curves and multivariate Cox analysis explained the potential prognostic significance of LINC00324 in cervical cancer. Significantly increased expression of LINC00324 and down-regulated miR-195-5p were negatively correlated in cervical cancer. Knockdown of LINC00324 inhibited the progression of cervical cancer, which was related to its mechanism of targeting and downregulating miR-195-5p. In addition, low expression of LINC00324 may prolong the survival period of patients with cervical cancer. LINC00324 targets miR-195-5p to regulate the progression of cervical cancer and have potential as a prognostic molecular marker for cervical cancer.

Survival of women with cervical cancer in East Africa: a systematic review and meta-analysis

The prognosis for cervical cancer varies greatly between nations. The disparity in cancer survival rates within nations is largely a result of disparities in public knowledge, the accessibility of cancer services, diagnosis and treatment. The purpose of this systematic review and meta-analysis is to assess the survival rate and associated factors among cervical cancer patients in East Africa. Literature search was carried out using Google scholar, PubMed/Medline, Embase and CINHAL. Covidence, a web-based program, was used to import studies for review process. PRISMA guidelines were followed. A total of 110 abstracts were identified from electronic sources. There were five duplicate articles removed. We looked at 105 papers' abstracts and titles, and we excluded 78 of them because they did not fit our inclusion criteria. We conducted a full-text analysis of the remaining 27 papers, leaving out 14 researches that did not fit our inclusion requirements. For final review, 13 studies were included. Using the Joanna Briggs Institute (JBI) assessment checklist, methodological quality was evaluated. The included articles were cohort studies. They were conducted in Ethiopia, Uganda, Zimbabwe, Kenya, Sudan, Tanzania and Rwanda. One-year, two-year, three-year, four-year and five-year overall survival rates ranged from 67% to 92%, 55% to 84%, 44% to 53%, 32% to 47%, and 26% to 43%, respectively. The pooled one-year, two-year, three-year, four-year and five-year survival rates of cervical cancer patients in East Africa were 84%, 71%, 50%, 39% and 36%, respectively. HIV status, late presentation, treatment modalities, older age and presence of comorbidities were the most commonly mentioned prognostic factors for survival. CRD42023402551.

Using robotic single-port vNOTES for gynaecological oncology: omentectomy in a patient with an ovarian granulosa cell tumor—a case study

Robotic single-port transvaginal natural orifice transluminal endoscopic surgery (RSP-vNOTES) is an emerging minimally invasive approach that combines the advantages of robotic surgery with scarless transvaginal access. Its application in gynecologic oncology remains limited, particularly for omentectomy during ovarian cancer staging. We present the case of a 45-year-old woman with an ovarian granulosa cell tumor (GCT) who underwent supplemental staging surgery following unilateral oophorectomy. Using a single-port robotic system via the transvaginal route, hysterectomy, right salpingo-oophorectomy, and omentectomy were performed. Key technical steps included enhanced visualization with gauze placement and use of an additional robotic arm for omental traction. The procedure lasted 2 hours and 10 minutes with an estimated blood loss of 50 mL. No intraoperative or postoperative complications occurred. The patient did not require postoperative analgesics and was discharged on postoperative day 3. Final pathology confirmed absence of omental metastasis. This case demonstrates the feasibility and safety of RSP-vNOTES for omentectomy in gynecologic oncology. The technique offers potential benefits including reduced abdominal trauma, faster recovery, and superior visualization for complex dissections. While further studies are necessary to validate long-term oncologic outcomes, RSP-vNOTES may represent a promising minimally invasive option for selected patients requiring ovarian cancer staging surgery.

Effects of vaginal dilation therapy on vaginal length, vaginal stenosis, vaginal elasticity and sexual function of cervical cancer survivors

Cervical cancer survivors can experience vaginal length shortening, vaginal stenosis, vaginal elasticity deterioration, sexual frequency reduction and sexual dysfunction. This prospective, uncontrolled, monocentric clinical interventional study aimed to evaluate the effect of vaginal dilation therapy on vaginal condition and sexual function of cervical cancer survivors who had not received timely vaginal dilation. A total of 139 patients completed the study. They received 6 months of vaginal dilation therapy. We evaluated their vaginal elasticity, vaginal diameter, vaginal length and sexual function before and after vaginal dilation therapy. Their vaginal conditions were evaluated by customised vaginal moulds, and the sexual function was assessed by female sexual function index. The SPSS 25 software was used to analyse all the data. Age, vaginal diameter and sexual intercourse frequency before diagnosis were significantly associated with female sexual dysfunction of the patients after cancer treatment. Vaginal dilation therapy improved vaginal stenosis, vaginal length and sexual function in all the patients; however, the vaginal elasticity and incidence of sexual dysfunction did not improve significantly. Sexual intercourse frequency before diagnosis, vaginal elasticity, time interval from last treatment and treatment modalities were significantly associated with the change in female sexual function index score before and after vaginal dilation therapy. Patients with a time interval from the last treatment less than 24 months or those who had moderate or good vaginal elasticity, benefitted more from vaginal dilatation therapy. Cervical cancer survivors who had not received timely vaginal dilation still benefitted from vaginal dilation therapy, irrespective of the treatment methods they received. Moreover, vaginal dilation therapy should be performed as early as possible after cervical cancer treatment.

The inflammatory markers combined with CA125 may predict postoperative survival in endometrial cancer

Endometrial cancer (EC) has a high latency, making prognosis difficult to predict. Cancer antigen 125 (CA125) is not specific as a tumour marker for EC; however, complete blood count (CBC) inflammatory markers are associated with prognosis in various malignancies. Thus, this study investigated the value of CBC inflammatory markers combined with CA125 levels in predicting the prognosis of patients with EC. In this study, 517 patients with EC were recruited between January 2015 and January 2022, and clinical characteristics, CBC inflammatory markers, and CA125 levels were assessed. Differences in each index at different EC stages and the correlation between the index and EC stage were analysed, and the influence of the index on EC prognosis was evaluated. Platelet distribution width (PDW) levels were significantly lower in patients with advanced EC than in those with early EC, whereas the systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and CA125 levels were significantly higher in patients with advanced EC (all P < 0.05). ROC curve and multivariate logistic regression analyses indicated that decreased PDW and increased CA125 levels were independent risk factors for EC staging progression. In addition, multivariate Cox regression analysis showed that the combination of low PDW and high CA125 (PDW + CA125 = 2) was an independent prognostic factor of survival in EC patients. Kaplan-Meier survival analysis indicated that patients with low PDW and high CA125 had worse overall survival. The PDW and CA125 score may be an independent prognostic factor for postoperative overall survival in patients with EC and a useful marker for predicting the prognosis of these patients.

Effect of ubiquitin-specific proteinase 43 on ovarian serous adenocarcinoma and its clinical significance

Ovarian cancer stands as a highly aggressive malignancy. The core aim of this investigation is to uncover genes pivotal to the progression and prognosis of ovarian cancer, while delving deep into the intricate mechanisms that govern their impact. The study entailed the retrieval of RNA-seq data and survival data from the XENA database. Outliers were meticulously excluded in accordance with TCGA guidelines and through principal components analysis. The R package 'deseq2' was harnessed to extract differentially expressed genes. WGCNA was employed to prioritise these genes, and Cox regression analysis and survival analysis based on disease-specific time were conducted to identify significant genes. Immunohistochemistry validation was undertaken to confirm the distinct expression of USP43. Furthermore, the influence of USP43 on the biological functions of ovarian cancer cells was explored using techniques such as RNA interference, western blotting, scratch assays, and matrigel invasion assays. The examination of immune infiltration was facilitated via CIBERSORT. The study unearthed 5195 differentially expressed genes between ovarian cancer and normal tissue, comprising 3416 up-regulated and 1779 down-regulated genes. WGCNA pinpointed 204 genes most intimately tied to tumorigenesis. The previously undisclosed gene USP43 exhibited heightened expression in tumour tissues and exhibited associations with overall survival and disease-specific survival. USP43 emerged as a driver of cell migration (43.27 ± 3.91% vs 19.69 ± 1.94%) and invasion ability (314 ± 32 vs 131 ± 12) through the mechanism of epithelial mesenchymal transition, potentially mediated by the KRAS pathway. USP43 was also identified as a booster of CD4+ T memory resting cell infiltration, while concurrently reducing M1 macrophages within cancer, thereby fostering a milieu with relatively immune suppressive traits. Interestingly, USP43 demonstrated connections with epigenetically regulated-mRNAsi, although not with mRNAsi. This study underscores the role of USP43 in facilitating tumour migration and invasion. It postulates USP43 as a novel therapeutic target for ovarian cancer treatment.

Septin9 DNA methylation as a promising biomarker for cervical cancer

Aberrant Septin9 methylation in cervical cancer has been rarely studied. We aimed to identify its diagnostic value in cervical cancer using cervical scrapings, and its predictive potential in plasma for pelvic nodal metastasis of cervical cancer. The statuses of methylated Septin9 in fresh cervical lesions and cervical scrapings were first evaluated by using quantitative methylation-specific PCR. Subsequently, the relationship between Septin9 methylation in 113 plasma samples and pelvic nodal metastasis of cervical cancer was evaluated. Methylated Septin9 was detected in all cancerous tissues, but not in cervicitis. The degrees of Septin9 methylation increased with growing severity of cervical lesions in cervical scrapings. The sensitivity of methylated Septin9 was lower than that of cytology, while it yielded a high specificity and area under the curve in detecting high-grade squamous intraepithelial lesion or cervical cancer; and when Septin9 methylation combined with HPV16/18 genotyping, the sensitivity would increase from 70.42% to 82.39%. Plasma-based Septin9 methylation had a high discriminatory power in predicting pelvic nodal metastasis of cervical cancer, with an optimal specificity of 81.48%. In conclusion, we demonstrated methylated Septin9 to be an innovative diagnostic biomarker for cervical cancer and its non-invasive predictive potential in plasma for pelvic nodal metastasis of cervical cancer.Impact statement

Rac3 promotes proliferation and invasion of endometrial cancer through the AKT/mTOR signalling pathway

Rac3 is associated with the malignancy of various tumours, including endometrial cancer (EC). Silencing Rac3 has been shown to effectively enhance the sensitivity of EC cells to chemotherapeutic drugs. Nonetheless, the underlying mechanism is still unclear. Firstly, the association between Rac3 and EC was verified through the TCGA database. Subsequently, Ishikawa cell lines with Rac3 knockdown were constructed. The effects of Rac3 knockdown on the growth, migration and invasion of Ishikawa cells were assessed through clone formation experiments, CCK-8 experiments, flow cytometry, and Transwell experiments. Finally, qRT-PCR and WB experiments were conducted to initially explore the potential mechanism of action of Rac3 in the development of EC. Compared with normal tissues, the expression of Rac3 in EC tissues was significantly elevated, and this expression further increased with the aggravation of tumour. In Ishikawa cells with Rac3 knockdown, cell viability was significantly reduced, the apoptosis rate increased, and the invasion and migration abilities of the cells were inhibited. Correlation analysis of EC samples revealed a positive correlation between Rac3 and AKT2, AKT3 and mTOR. Additionally, WB and qRT-PCR also suggested that the mechanism of action of Rac3 in the development of EC may be related to the upregulation of AKT2, AKT3 and mTOR. Knockdown of Rac3 may inhibit the occurrence and development of EC, which is related to its inhibition of AKT2, AKT3 and mTOR. This discovery provides a theoretical basis for clinical screening of biomarkers for EC and the development of potential therapeutic targets.

Publisher

Informa UK Limited

ISSN

0144-3615