The frequent omental metastasis of ovarian cancer (OvCa) at initial diagnosis is due to the omental premetastatic microenvironment, which is rich in activated fibroblasts. However, the molecular events driving the phenotypic transformation of omental fibroblasts that favor metastasis remain largely unexplored. Previously, we found that tumoral enhancer of zest homolog 2 (EZH2), a key epigenetic regulator catalyzing trimethylation at H3K27, played a crucial role in OvCa metastasis. In this study, we revealed that extracellular vesicles (EVs) derived from EZH2-high OvCa cells induce the expression of Periostin (POSTN), but not α-SMA, in omental fibroblasts, facilitating tumor metastasis. Nude mice with intraperitoneal injection of EVs before tumor cell inoculation showed that EVs derived from EZH2-high ovarian cancer cells promote omental metastasis. Human primary omental fibroblasts cocultured with EVs, especially those derived from EZH2-high OvCa cells, exhibited boosted migration, invasion capacities and conditioned medium from EV-activated fibroblasts promotes cancer cell migration, invasion and proliferation. These results may provide novel insight into EZH2-targeted therapy for ovarian carcinoma with intraperitoneal dissemination.

Ovarian cancer stem cells (OCSCs) play a pivotal role in the initiation, maintenance, and progression of ovarian cancer, functioning through complex molecular mechanisms that are closely linked to metastasis and drug resistance. The complexity of these underlying mechanisms contributes to cancer hallmarks such as the high plasticity of OCSCs, leading to chemotherapy resistance; activation of invasion and metastasis, epigenetic reprogramming, and cell death resistance; and deregulation of cellular metabolism. OCSCs are characterized by the expression of markers including ALDH, CD133, CD44, and CD24. They preserve their stemness through intricate molecular mechanisms that involve interactions with the tumor microenvironment and various signaling pathways. To investigate these molecular mechanisms, both in vitro and in vivo models of OCSC have been established. The results of these studies can be applied in clinical practice, facilitating the development of various new therapies. This review aims to provide a deeper understanding of the mechanisms through which OCSCs function, highlighting significant opportunities for future research aimed at improving ovarian cancer treatment.

PARP inhibitor (PARPi)-based synthetic lethal therapies have displayed limited benefits in BRCA-proficient ovarian cancer. To potentiate the application of PARPi, an ultrasound contrast agent OLA-NDs for delivery of the PARPi olaparib (OLA) was established for enhancing DNA damage by blocking DNA repair. OLA-NDs were endowed with endogenous pH- and exogenous ultrasound (US)-responsiveness to target tumors, as well as contrast-enhanced US imaging for diagnostic and therapeutic integration. OLA-NDs could upregulate NOX4 to induce oxidative stress and sensitize BRCA wild-type A2780 cells to DNA oxidative damage through the utilization of ultrasound-targeted microbubble destruction (UTMD). In addition, the strategy further increased ROS production by interfering with mitochondrial function, thereby exacerbating DNA double-strand breaks (DSBs) and inducing mitochondria-mediated apoptosis. As a consequence, the combined application of UTMD and OLA-NDs demonstrated significant antitumor effects in vitro and in vivo. This combined strategy of amplifying oxidative damage improved lethality by promoting DNA DSBs and apoptosis with reduced adverse side effects, which would provide new insight for the clinical application of PARPi in BRCA-proficient ovarian cancer.

Symptoms occur in up to 75% of patients with early-stage ovarian cancer; as such, using a symptom inventory (SI) to stratify which patients should receive screening for ovarian cancer is an attractive approach to mitigate false-positives. We report on the feasibility and results of a prospective four-question SI that assessed the following symptoms: abdominal pain, bloating, early satiety, and urinary complaints. Frequency and duration of symptoms were not assessed.

A SI was added to the standard pre-appointment check-in process via the electronic medical record's (EMR) patient portal for all annual or new patient visits in a generalist obstetrics and gynecology faculty practice in patients over 40 years of age. IRB exemption was granted. Data were extracted from the EMR, compiled in REDCap, and analyzed in R.

A total of 589 individual patients were included in the final analysis. The median age of the participants was 50 years (range: 40-86). 27.8 % of patients experienced at least one symptom in the prior year, and the most commonly reported symptom was urinary urgency/frequency (14.9 %). Patients with a history of medical comorbidities such as depression, uterine fibroids, endometriosis, and irritable bowel syndrome were more likely to screen positive on the SI. No cancers have been diagnosed to date.

Implementing a SI using the EMR is feasible but is influenced by the presence of pre-existing diagnoses. The effectiveness of an EMR-based SI pre-screen as a selection criterion for early detection requires further study and assessment of frequency and duration of symptoms should be considered.

To explore the feasibility of Dual-Energy Computed Tomography (DECT) in distinguishing metastatic from non-metastatic lymph nodes (LNs) in ovarian High-Grade Serous Carcinoma (HGSC), and to assess the incremental diagnostic value of combining DECT with morphologic parameters in differentiating metastatic and non-metastatic LNs.

From October 2021 to May 2024, 141 LNs from 39 patients with HGSC who underwent DECT were retrospectively enrolled. LNs were matched with the pathological report. Five morphologic parameters and nine DECT parameters were assessed. DECT parameters were obtained from both the arterial and venous phases, including the attenuation at 40 and 70 keV, slope of the spectral Hounsfield unit curve (λHu), Virtual Non-Contrast (VNC), Iodine Concentration (IC), Normalized Iodine Concentration (NIC), electron density (Rho), effective atomic number (Zeff) and Dual-Energy Index (DEI). Independent-sample Student's t test was used to compare continuous variables, while multivariable binary logistic regression analyses was applied to identify independent predictors for LN metastasis in the morphology, DECT, and combined models. Receiver Operating Characteristic (ROC) analysis was performed to evaluate the diagnostic performance of these three models in differentiating metastatic from non-metastatic LNs.

86 metastatic LNs and 55 non-metastatic LNs were finally enrolled in our study. The short diameter (S), long diameter (L), and S/L ratio were significantly larger in metastatic LNs compared to non-metastatic LNs (9.69 ± 4.06 vs. 6.37 ± 1.24 mm, P < 0.001; 13.99 ± 5.36 vs.9.61 ± 2.30 mm, P < 0.001; 0.70 ± 0.15 vs. 0.67 ± 0.12, P = 0.023). In the venous phase, λHU, VNC and Rho were significantly higher in metastatic LNs compared to non-metastatic LNs (-3.596 ± 1.115 vs. -4.234 ± 1.077, P = 0.001; 24.242 ± 9.867 vs. 15.826 ± 11.830, P < 0.001; 32.557 ± 8.023 vs. 26.936 ± 9.420, P < 0.001), while IC, NIC, Zeff, DEI were significant lower in metastatic LNs than non-metastatic LNs (1.872 ± 0.678 vs. 2.404 ± 1.140, P = 0.001; 38.309 ± 14.443 vs. 47.247 ± 22.270, P = 0.005; 8.513 ± 0.320 vs. 8.719 ± 0.360, P = 0.001; 0.014 ± 0.006 vs. 0.018 ± 0.007, P = 0.045). The Area Under the Curve (AUC) of morphology model and DECT model were 0.793 (95 %CI: 0.721-0.862) and 0.762(95 %CI: 0.690-0.825), respectively. The combination of the morphology model and DECT model revealed optimal diagnostic performance (AUC = 0.845; 95 %CI: 0.780-0.896), which was significantly higher than that of the individual models (P = 0.015, P = 0.006, respectively).

DECT parameters provide incremental diagnostic value in assessing metastatic LNs in patients with HGSC. The combination of the morphology and DECT models significantly improves diagnostic performance compared to the standalone morphology model.

While excess body fatness in older adulthood has been linked to ovarian cancer, the influence of changes in body fatness over time is unclear. This study examined the association between adulthood trajectories of body mass index (BMI), a proxy for body fatness, and ovarian cancer.

In a population-based case-control study (440 cases, 820 controls), we used a group-based trajectory approach to identify BMI trajectories from age 20-70. Using unconditional logistic regression, we estimated adjusted odds ratios (aOR) and 95 % confidence intervals (95 % CI) for the associations between the estimated trajectories and ovarian cancer.

We identified three distinct BMI trajectories: a normal-stable trajectory, a normal-to-overweight trajectory and an overweight-to-obese trajectory, which included 63.2 %, 31.0 % and 6.8 % of the population, respectively. Multivariable aORs suggested that participants with normal weight at the onset of adulthood who became overweight over their adulthood time did not differ in their risk of ovarian cancer compared to those who maintained a normal weight throughout adulthood (aOR (95 %CI): 0.89 (0.69-1.16)). Among those in the overweight-to-obese trajectory, the aOR (95 %CI) was 1.45 (0.87-2.43), and thus in the direction of an increased ovarian cancer risk compared to those who maintained a normal weight.

Our findings underscore the need for further research to clarify the role of body fatness across the lifetime in the etiology of ovarian cancer.

Cancer development is driven by genetic alterations, particularly cancer driver mutations (CDMs), which are associated with aggressive phenotypes and shorter survival. In contrast, higher mutation loads caused by microsatellite instability (MSI) or mismatch repair deficiency (MMRd) can induce anti-cancer immunity, leading to tumor shrinkage and improved responses to immune checkpoint inhibitor (ICI) therapies. However, understanding how CDMs and MSI/MMRd influence cancer evolution remains limited. We opted uterine corpus endometrial carcinoma (UCEC) as a model in this study due to its MSI-high/MMRd characteristics. Somatic mutation screening revealed that UCEC has a significantly higher mutation rate in cancer driver genes compared to ovarian cancer (OVCA) and cervical squamous cell carcinoma (CSCC), despite these cancers arising from histologically connected organs in the reproductive tract. Interestingly, these CDMs did not necessarily drive tumor progression. Using a cutoff of 7.0 (mutations/Mb) for tumor mutation burden (TMB), we classified UCEC patients into two groups with distinct clinical features, genetic profiles, and drug sensitivities. Among the known CDMs, TP53 mutations and their functional networks emerged as key drivers in UCEC progression, while mutations in CTNNB1, PTEN, and ARID1A may enhance anti-tumor immunity, correlating with longer overall survivals. Drug screening using GDSC and CTRPv2 databases suggested that GSK-3 inhibitor IX may be effective for treating aggressive UCEC patients with a non-MSI phenotype. Curcumin showed efficacy for UCEC patients with MSI, especially with ICI therapy. Our study highlights the importance of immune regulation and tolerance over CDMs in cancer development, particularly in those with an MSI-high/MMRd phenotype. We propose that TMB could serve as a valuable screening method alongside molecular and histopathological classifications to guide treatment strategies for UCEC patients.

Circular RNAs (circRNAs) have emerged as promising biomarkers and therapeutic targets in gynecological cancer. The present review explored developments in circRNA research in ovarian, endometrial and cervical cancer. circRNA biogenesis, functions and roles in cancer pathogenesis have been discussed, focusing on their potential as diagnostic and prognostic markers. Furthermore, circRNAs mechanisms of action, including miRNA sponging, protein scaffolding and peptide encoding were examined, highlighting specific circRNAs implicated in each cancer type and their clinical significance. The unique properties of circRNAs, such as stability and tissue-specific expression, make them ideal candidates for biomarker development. By synthesizing the currently available literature and identifying future research directions, the present review underscored circRNAs potential to improve gynecological cancer management through novel diagnostic tools, prognostic markers and targeted therapies.

A patient decision aid on opportunistic salpingectomy and salpingectomy as a sterilization method has been developed to provide uniform counseling and reduce practice variation. The aim of this study was to evaluate the use of the patient decision aid in daily clinical practice to ensure its effectiveness and usability, as well as its influence on the decision-making process and the decision of opportunistic salpingectomy.

As part of the STOPOVCA-implementation study, we conducted a multicenter observational study in 16 hospitals between July 2020 and February 2024. Patients who were eligible for opportunistic salpingectomy were invited to use the decision aid while they considered whether or not to undergo opportunistic salpingectomy. Digital questionnaires were used to evaluate the decision aid, the decision process, and patients' decisions 6-8 weeks post-surgery.

425 out of 542 patients participated in the questionnaire. A majority of these 425 patients received (N = 357; 84%) and used the decision aid (N = 347; 82%). Two thirds (N = 234; 67%) of those who used the decision aid stated that it increased their knowledge of opportunistic salpingectomy. Patients considered the decision aid a usable aid, allocating a score of 8.1 out of 10 and would recommend it to other patients facing the decision regarding opportunistic salpingectomy. Patients considered the extent to which they were involved in the decision-making process as high, and the decisional conflict low. The majority of patients who used the decision aid opted for opportunistic salpingectomy (N = 326; 95%). Main reasons for choosing opportunistic salpingectomy were the risk-reducing effect of ovarian cancer (N = 311; 90%) and the lack of functionality of the fallopian tubes after childbearing (N = 320; 92%).

The patient decision aid was used by a majority of patients who received it. The decision aid was regarded by patients as user-friendly, and it was recommended to be used in the decision-making process for opportunistic salpingectomy. Patients stated that the decision aid provides reliable information and increases patients' knowledge of opportunistic salpingectomy.

Extensive peritoneal metastasis and malignant ascites continue to pose substantial challenges in achieving favorable treatment outcomes for ovarian cancer. Berberine (BBR), an active component of numerous traditional Chinese herbs, has demonstrated potent anti - tumor effects across various malignancies, including ovarian cancer. In this study, we comprehensively evaluated the impact of BBR on the growth and metastasis of ovarian cancer both in vitro and in vivo. RNA - sequencing was employed to elucidate the underlying mechanisms. Specifically, we investigated lipid metabolism and mitochondrial function in ovarian cancer cells and mice, comparing BBR - treated and untreated groups. Additionally, CIBERSORT analysis and immunohistochemical (IHC) staining were utilized to confirm BBR's ability to enhance the infiltration of tumor-infiltrating immune cells into adipose tissue and improve the inflammatory tumor microenvironment. Our findings indicate that BBR significantly inhibits the growth and metastasis of ovarian cancer in vitro and in vivo. The effects can be attributed to two key processes. Firstly, BBR suppresses the lipid metabolism by downregulating lipid uptake related receptor CD36, lipid metabolic enzyme and mitochondrial function. Secondly, BBR alleviates the aging of adipose tissue and adipose derived stem cells (ADSCs), thereby decreasing the secretion of senescence-associated secretory phenotype (SASP). These ultimately lead to the increasing the improvement of tumor infiltrating immune cells, such as CD4⁺ helper T cells (CD3⁺CD4⁺) and cytotoxic T lymphocytes (CD3⁺CD8⁺), and inflammation in ovarian cancer tissue. Collectively, these findings suggested a potential therapeutic effect of BBR in the treatment of advanced ovarian cancer, particularly cases complicated by peritoneal metastasis and malignant ascites.

Triphenyl phosphonium conjugated amphiphilic peptides are self-assembled into micelles that show potential antimicrobial activity against drug resistant strains. Moreover, these peptides destroy ovarian cancer cells through mitochondrial reactive oxygen species (ROS) generation while maintaining cytocompatibility with HEK 293 (non-cancerous) cells, indicating the emergence of biomaterials with anticancer and antimicrobial activities.

Ovarian cancer is one of the most common malignancies of the female reproductive system and is associated with poor prognosis. This study aimed to utilize single-cell RNA sequencing to investigate the heterogeneity of malignant epithelial cells in ovarian cancer, focusing on their potential functions and the implications for treatment and prognosis.

Single-cell RNA sequencing data were clustered using a single-cell transcriptome clustering method, and malignant epithelial cells were identified through copy number variation analysis. The interaction patterns between different malignant subpopulations and immune/stromal cells were analyzed using cell-to-cell communication analysis. A risk score (URS) model based on the UBE2C + epithelial subpopulation was then constructed through LASSO and multivariable Cox regression. High and low URS groups were compared in terms of tumor mutational burden (TMB), survival outcomes, and drug sensitivity. Finally, the role of GTF2F2 in ovarian cancer progression was validated through gene knockdown experiments in an ovarian cancer cell line (ES-2).

Three major malignant epithelial cell subpopulations were identified (TMSB4X + Epi, TSC22D1 + Epi, and UBE2C + Epi). The UBE2C + Epi subpopulation exhibited higher stemness and greater invasive potential. The constructed URS model effectively stratified patients into high- and low-risk groups, with the high-risk group displaying a higher TMB level (p = 0.00011). Drug sensitivity predictions indicated that osimertinib, rapamycin, and dihydrorotenone might have stronger inhibitory effects in the high-risk group, whereas ERK inhibitors were more effective in the low-risk group. Functional assays demonstrated that GTF2F2 knockdown significantly suppressed ovarian cancer cell migration and invasion. Western blot analyses further showed elevated E-cadherin and reduced N-cadherin expression, suggesting that GTF2F2 may promote epithelial-mesenchymal transition (EMT).

The risk score model established in this study offers a novel framework for patient stratification and personalized therapy. Notably, the identification of the UBE2C + Epi subpopulation and key genes such as GTF2F2 highlights potential diagnostic and therapeutic targets, shedding light on the pathogenesis of ovarian cancer and paving the way for precision medicine approaches.

Ovarian malignancies overexpress estrogen receptors (ERs), offering a therapeutic avenue for targeted drug delivery. Here, we developed a novel ER-targeted PEGylated liposome (ES-SSL-PTX/CDDP) coencapsulating paclitaxel (PTX) and cisplatin (CDDP) to enhance therapeutic efficacy and mitigate systemic toxicity. ES-SSL-PTX/CDDP exhibited a spherical shape with a hydrodynamic diameter of around 150 nm, a negative zeta potential of about -20 mV, and high encapsulation efficiencies of 83.7% for PTX and 41.1% for CDDP. ES-SSL-PTX/CDDP showed a sustained release pattern, with release rates of <60% for both drugs within 12 h. Meanwhile, ES-SSL-PTX/CDDP demonstrated excellent storage and serum stability, with the leakage rates less than 30% when stored at either 4 or 25 °C. ES-SSL-PTX/CDDP exhibited a strong antitumor effect in athymic mice with the tumor volume 8.50 times smaller than that in the control group on the 27th day, and the tumor inhibition rate reached 87.3%. Pharmacokinetic studies revealed prolonged circulation of ES-SSL-PTX/CDDP, with elimination half-lives (t1/2β) of 13.84 h (PTX) and 7.18 h (CDDP), which were 8.82- and 1.83-fold higher than those of PTX/CDDP, and clearance rates reduced to 0.01 L/h/kg (PTX) and 0.02 L/h/kg (CDDP), being 18.0- and 4.0-fold lower than those of PTX/CDDP. Acute toxicity results demonstrated a 2.12-fold increase in the LD50 of ES-SSL-PTX/CDDP (27.82 mg/kg for PTX; 19.87 mg/kg for CDDP) versus PTX/CDDP. Long-term toxicity studies demonstrated that ES-SSL-PTX/CDDP attenuated myelosuppression and nephrotoxicity, with no histopathological abnormalities observed across 32 tissues after 16 weeks of administration. This study highlights the potential of ES-SSL-PTX/CDDP to improve the efficacy and reduce the toxicity of platinum-taxane regimens in the treatment of ovarian cancer.

Ovarian cancer (OC) poses significant treatment challenges due to late-stage diagnosis and a complex tumor microenvironment contributing to therapy resistance. We optimized a U-CUP perfusion-based bioreactor method to culture patient-derived primary and metastatic OC specimens, demonstrating that perfusion better preserves cancer cell viability and proliferation, both when fresh and slow-frozen tissues were used. Perfused cultures maintained key microenvironment components, including cancer-associated fibroblasts, endothelial and immune cells. Genetic analysis confirmed the retention in culture of tumor-specific driver mutations. We hence challenged ad hoc generated cisplatin-sensitive and resistant OC cells with cisplatin during growth in U-CUP, validating our system for the testing of drug response. Finally, treatment of slow-frozen OC tissues with carboplatin/paclitaxel revealed different degrees of response to treatment, as indicated by variations in tumor necrosis and number of residual PAX8+ cells, providing the bases for the prompt evaluation of OC standard chemotherapy efficacy in our ex vivo system.

Ovarian cancer (OC) is one of the most severe cancers worldwide. Recent research suggests that the lysosomal pathway could be applied for early disease screening, prognosis evaluation, and adjuvant therapy. However, whether lysosome-related genes were applied for immune and prognosis prediction in OC remains unclear. RNA sequencing datasets, including clinical information of OC patients, were collected from TCGA and GEO databases. Lysosome-related prognostic genes and functional pathways in OC were identified using the lysosome dataset. The prognostic value of the most significant lysosome-related gene, SLAMF7, was estimated using Kaplan-Meier survival analysis. Differences in genomic mutations, tumor microenvironment immune infiltration, and drug resistance were evaluated in the high/low SLAMF7 of OC patients. The effect of SLAMF7 overexpression on the malignant characteristics of OC was assessed using OC cell lines (HEY A8 and OVCAR3 cells) and a xenograft mouse model. Based on the functional prediction of lysosome-related genes, T cell activation, immune receptor activity, and lysosomal pathways were significantly enriched in OC. Dimensionality reduction analysis using the random survival forest method confirmed that SLAMF7 was the most significantly different lysosome-related prognostic gene in OC. SLAMF7 was downregulated in OC cells and was associated with poor prognosis in OC patients. Low SLAMF7 expression was positively associated with chemotherapy sensitivity, immune infiltration, and function in OC patients. Overexpression of SLAMF7 promoted the pro-CTSB and LAMP1 expression, and inhibited CTSD expression in HEY A8 and OVCAR3 cells. Overexpression of SLAMF7 inhibited proliferation and formation of subcutaneous tumors in nude mice. The lysosome-related gene SLAMF7 is downregulated in OC and could serve as a prognostic biomarker. Overexpression of SLAMF7 inhibited the malignant of OC cells and tumor formation.

Poly adenosine-diphosphate-ribose polymerase (PARP) inhibitors (PARPi) have been approved to act as first-line maintenance (FL-M) therapy and as platinum-sensitive recurrent maintenance (PSR-M) therapy for ovarian cancer in China for >5 years. Herein, we have analyzed the clinical-application characteristics of olaparib and niraparib in ovarian cancer-maintenance therapy in a real-world setting to strengthen our understanding and promote their rational usage.

A retrospective chart review identified patients with newly diagnosed or platinum-sensitive recurrent ovarian cancer, who received olaparib or niraparib as maintenance therapy at Sichuan Cancer Hospital between August 1, 2018, and December 31, 2021. Patient medical records were reviewed. We grouped and analyzed patients based on the type of PARPi they used (the olaparib group and the niraparib group) and the line of PARPi maintenance therapy (the FL-M setting and the PSR-M setting). The primary endpoint was the 24-month progression-free survival (PFS) rate.

In total, 131 patients (olaparib: n = 67, 51.1%; niraparib: n = 64, 48.9%) were enrolled. Breast cancer susceptibility genes ( BRCA ) mutations ( BRCA m) were significantly less common in the niraparib group than in the olaparib group [9.4% (6/64) vs . 62.7% (42/67), P <0.001], especially in the FL-M setting [10.4% (5/48) vs . 91.4% (32/35), P <0.001]. The 24-month progression-free survival (PFS) rates in the FL-M and PSR-M settings were 60.4% and 45.7%, respectively. In patients with BRCA m, the 24-month PFS rates in the FL-M and PSR-M settings were 62.2% and 72.7%, respectively.

Olaparib and niraparib were effective in patients with ovarian cancer without any new safety signals except for skin pigmentation. In patients with BRCA m, the 24-month PFS of the PARPi used in the PSR-M setting was even higher than that used in the FL-M setting.

Platinum-based chemotherapy and debulking surgery is the standard of care for patients with advanced tubo-ovarian high-grade serous carcinoma (HGSC). The chemotherapy response scoring (CRS) system is a histopathologic scoring system developed to measure response to neoadjuvant chemotherapy with prognostic implications. Omental samples with high CRS have greater inflammatory cell infiltrates, but the immunophenotype of infiltrating immune cells and PD-L1 expression of the residual tumor has not been well-defined.

Twenty cases of patients with FIGO stage IIIA to IIIC HGSC undergoing interval debulking after receiving 3-4 rounds of chemotherapy were selected. 6/20 cases of omental samples were graded as CRS 1, 7/20 were graded CRS 2, and 7/20 were graded CRS 3. The following immunohistochemical stains were performed: CD8, CD4, Foxp3, PD1, and PD-L1. The total number of tumor-infiltrating lymphocytes was recorded, and each case was given a PD-L1 combined positive score (CPS) and tumor proportion score (TPS).

There was a significantly greater number of CD8+ T cells, PD-1+ T cells, CD4+ T cells, and Foxp3+ T cells in CRS 3-scored cases compared to CRS 1 scored cases (p-values: 0.0018, 0.0224, 0.0071, and 0.0136, respectively). CRS 3-scored cases had a greater PD-L1 CPS (CRS 3 CPS 13 ± 8.2 versus CRS 1 CPS 0 ± 0; p-value: 0.0485).

Tubo-ovarian high-grade serous carcinoma with greater response to neoadjuvant treatment have significantly greater T cell infiltrate and greater PD-L1 combined positive score, highlighting a potential role of the CRS as a predictive biomarker for immune checkpoint blockade therapy.

To study the pathological contribution of fatty acid (FA) metabolism regulators including fatty acid binding protein 4 (FABP4), FABP5, peroxisome proliferator-activated receptor alpha (PPARα), and PPARγ in ovarian carcinoma, non-cancerous human ovarian surface epithelium (HOSE) cells and two epithelial ovarian carcinoma (EOC) cell lines, AMOC-2 and ES2 established from ovarian serous adenocarcinoma and ovarian clear cell carcinoma, respectively, were subjected to (1) an analysis of the physical properties of spheroids, (2) qPCR analysis, (3) cellular metabolic analysis, and (4) multiomic pan-cancer analysis using the Cancer Genome Atlas (TCGA). In contrast to globe-shaped spheroids of HOSE cells, AMOC-2 and ES2 cells formed non-globe-shaped spheroids and ES2 spheroids were much more fragile than AMOC-2 spheroids. Gene expression levels of FABP4 and FABP5 in AMOC-2 cells and those of PPARγ in AMOC-2 cells were significantly higher than those in HOSE cells. Metabolic phenotypes and the effectiveness against antagonists for regulators were significantly different in the two types of cancerous cells. Those regulators were identified by a multiomic pan-cancer analysis as novel factors for the prediction of the prognosis of ovarian serous adenocarcinoma. The results show that dysregulated FA metabolism in AMOC-2 and ES2 suggests that the regulation of FA metabolism may be a critical factor in the pathogenesis of EOC.

S. Plasma lipids in circulation are integral to the physiopathological processes of the ovary and may impact the development of various ovarian conditions, including ovarian cancer (OC). This study utilized a two-sample Mendelian randomization method to examine the causal link between changes in 179 plasma lipid groups and ovarian cancer (OC) to gain deeper insights into this association. We used the inverse variance weighted (IVW) method as the main tool for analysis. We utilized statistical data from plasma lipidomics involving 7,174 Finnish individuals and OC data from the FinnGen consortium, including 2,339 European OC patients and 222,078 European healthy controls. Our analysis revealed that elevated levels of four plasma lipids-Phosphatidylcholine (14:0_16:0, O-18:2_18:2, 16:0_20:4)-are linked to an increased risk of OC, while Sphingomyelin (d34:2) seems to act as a protective factor(all P < 0.05). We also conducted tests for heterogeneity and pleiotropy in the MR results. Additionally, reverse MR analysis indicated that OC does not affect plasma levels of these lipids. To determine whether the observed significant plasma lipids influence OC through common risk factors, we selected BMI as a confounder for multivariable Mendelian randomization (MVMR) analysis. The results showed that Sphingomyelin (d34:2) levels remained significantly associated with OC even after including BMI as an exposure factor. Furthermore, we investigated whether these four lipids mediated the effect of BMI on OC but found no evidence supporting their mediating role. In summary, our findings confirm a causal link between certain plasma lipid species and OC, providing fresh perspectives for risk evaluation and potential therapeutic strategies.

Global epidemiological reports indicate a steady increase in the tendency to develop ovarian cancer. The symptoms of ovarian cancer are non-specific, and there is no effective screening tool. Most often, surgery, chemotherapy, and radiotherapy, alone or in combination, are used to treat ovarian cancer. We have a better understanding of the biology of ovarian cancer, the genetic basis of hereditary ovarian cancer, the stage of the disease, and the role of cytoreductive surgery and more effective chemotherapy, which translates into an increase in the percentage of patients who survive 5 years after diagnosis. A growing body of evidence points to the role of genetic factors in the development of cancer. It is known that mutations in the BRCA1 gene are responsible for an increased risk of developing ovarian cancer. The role of other genetic disorders, such as polymorphic variants, in increasing the risk of developing cancer is still being investigated. Ovarian cancer is a hormone-dependent cancer and its steroid hormones are estrogens. Estrogens affect cells through the estrogen receptors ERα and ERβ. An imbalance between ERα and ERβ receptor expression may, therefore, be a key step in estrogen-dependent carcinogenesis. In 60% of cancer cases, significantly elevated levels of ERα receptors are detected. The ERα receptor is encoded by the ESR1 gene, so its polymorphisms can be considered molecular markers of ovarian cancer. This article discusses the epidemiology, pathogenesis, risk factors, genetic testing, treatment, and diagnosis of ovarian cancer, as well as providing an overview of standard treatment approaches and new, targeted biologic therapies.

High-grade serous ovarian cancer (HGSOC) remains an urgent unmet clinical need, with more than 70% of patients presenting with metastatic disease. Many patients develop large volumes of ascites, which promotes metastasis and is associated with poor therapeutic response and survival. Immunotherapy trials have shown limited success, highlighting the need to better understand HGSOC immunology. Here, we analyzed cytotoxic lymphocytes [natural killer (NK), T, and innate T cells] from patients with HGSOC and observed widespread dysfunction across primary and metastatic sites. Although nutrient rich, ascites was immunosuppressive for all lymphocyte subsets. NK cell dysfunction was driven by uptake of polar lipids, with associated dysregulation in lipid storage. Phosphatidylcholine was a key immunosuppressive metabolite, disrupting NK cell membrane order and cytotoxicity. Blocking lipid uptake through SR-B1 protected NK cell antitumor functions in ascites. These findings offer insights into immune suppression in HGSOC and have important implications for the design of future immunotherapies.

The treatment of epithelial ovarian cancer (EOC) is evolving towards personalization and precision. Early prediction of recurrence can provide a basis for individualized monitoring and treatment. Our study aims to develop a predictive model for early recurrence of ovarian cancer incorporating Traditional Chinese Medicine (TCM) treatment.

We reviewed the clinicopathological and prognostic data of EOC patients who achieved complete clinical remission after surgery and chemotherapy at Guangdong Traditional Chinese Medicine Hospital (GPHCM) between December 2011 and July 2022. Basic information, clinical characteristics, treatment plans, and follow-up data were collected. Univariate logistic analysis was performed to identify significant variables (P<0.10), followed by Least Absolute Shrinkage and Selection Operator (LASSO) regression to further determine key risk factors. A multivariate logistic regression model was constructed based on these factors, and a nomogram was developed to predict recurrence risk. The model's effectiveness was internally validated using bootstrap resampling (1000 iterations) and assessed for discrimination and calibration using Area Under Curve (AUC), the Hosmer-Lemeshow test, and calibration plots. Additionally, decision curve analysis (DCA) was performed to evaluate the clinical utility of the model.

This study included a total of 170 patients. Multivariate logistic regression analysis revealed that surgical procedure, The International Federation of Gynecology and Obstetrics (FIGO) stage, completion of the full chemotherapy course, and exposure to TCM were independent prognostic factors for ovarian cancer recurrence. Based on these factors, this study developed a nomogram model to predict recurrence risk, incorporating four key variables. The AUC of the prediction model was 0.843 (95% CI: 0.774-0.898), and the Hosmer-Lemeshow test and calibration plot indicated good calibration. DCA showed the model provided higher net benefit across a wide range of threshold probabilities.

The nomogram we developed effectively predicted 2-year recurrence risk in epithelial ovarian cancer patients. Notably, TCM treatment lasting more than 6 months may help prolong progression-free survival (PFS).

Metabolic reprogramming is a hallmark of cancer and de novo lipogenesis (DNL) accelerates the progression of ovarian cancer. In this study, we investigated the effects of cardamonin, a natural compound potential to suppress various malignancies, on the lipid anabolism in ovarian cancer. Cell proliferation was assessed using CCK-8 and clone formation assay. Cell apoptosis was detected by flow cytometry with Annexin V-FITC/PI staining and mitochondrial membrane potential (MMP) was measured with JC-10 probe. Free fatty acids (FFA) was measured by fluorescence using acyl-CoA oxidation and carnitine palmitoyl transferase-1 (CPT-1) activity was analyzed by spectrophotometric assay using palmitoyl-CoA and DTNB (5,5'-dithio-bis-(2-nitrobenzoic acid)) reaction. mRNA expression was measured by Quantitative Real-Time PCR. Protein expression was analyzed through western blotting and immunofluorescence. Raptor was knocked down by shRNA and Raptor was overexpressed by lentiviral transfection. The antitumor effect of cardamonin was evaluated using a xenotransplantation tumor bearing mouse model. Cardamonin suppressed the cell proliferation, induced cell apoptosis and triggered mitochondrial damage in ovarian cancer cells. Cardamonin inhibited the protein expression of sterol regulatory element binding protein 1 (SREBP1) and its downstream lipogenic enzymes and decreased FFA content and CPT-1 activity. Additionally, cardamonin inhibited the activation of mechanistic target of rapamycin complex 1 (mTORC1) and expression of regulatory-associated protein of mTOR (Raptor). Raptor knockdown abolished the inhibitory effect of cardamonin on mTORC1 and SREBP1. Furthermore, cardamonin inhibited mTORC1 activation and lipogenic proteins expression induced by Raptor overexpression. Cardamonin reduced the tumor growth and fatty acid synthase of the tumors, as evidenced by decreased expression of Ki-67 and FASN. It suggests that cardamonin suppresses mTORC1/SREBP1 through reducing the protein level of Raptor and inhibits DNL of ovarian cancer.

Recent reports of the Golestan population-based cancer registry (GPCR) suggested increasing trends in the incidence and survival rates of cancers in Golestan, Northern Iran. We investigated the risk of developing second primary neoplasms (SPNs) among cancer survivors in Golestan.

The GPCR cases for whom a first primary cancer was diagnosed between 2004 and 2019 were included as cohort participants. The cohort members were followed by the end of 2020, and the occurrence of a second primary neoplasm (SPN) was considered as the study outcome event. The standardized incidence ratios (SIRs) and the Absolute excess risks (AERs), with corresponding 95% confidence intervals (95% CI) were calculated to evaluate the risk of SPNs.

Of the total 32,980 cases with first primary cancer, with a median follow-up of 3.4 years, 772 (2.3%) SPNs were registered. Our findings suggested a significantly higher risk of occurring new neoplasms among cancer survivors, with a SIR of 4.6 (95% CI: 4.3-4.9) and an AER of 41.8 per 10,000 person-years (95% CI: 37.6-46.0). Rural residents had a higher risk of SPN (SIR = 5.48) than urban dwellers (SIR = 3.99). Patients with first primary cancers of the ovary (SIR = 6.83) and prostate (SIR = 6.72) had the highest risk of any SPNs. The highest risk of site-specific SPNs was observed for the SPNs of the ovary (SIR = 8.11) and NHL (SIR = 7.07).

Our results suggest that cancer patients are at significantly higher risk of getting a new neoplasm than the general population. These findings highlight the need for designing and implementing efficient surveillance programs for cancer survivors.

To determine differentiating CT imaging features of primary ovarian cancers from ovarian metastases of gastrointestinal origin.

Retrospective study of 50 patients with new ovarian lesions on CT, half were primary ovarian cancers and half gastrointestinal metastases. Two blinded independent readers described tumor characteristics on CT (size, laterality, margin, etc.) and ancillary features (ascites, peritoneal seeding, lymphadenopathy, etc.). Patient age, sex, cancer history, and tumor marker levels for CA-125 and CEA were collected. Wilcoxon test and Pearson's chi-squared test were used for statistical analysis.

50 patients with mean age of 62.1 years were included. Ovarian metastases were more likely to be cystic/mainly cystic (p=0.013), have smooth margins (p=0.011), and have no/mild enhancement (p<0.001). Primary ovarian lesions were associated with moderate to large volume of ascites (p=0.047) and more commonly seen with lymphadenopathy (p=0.008). Laterality was not significantly different between the two groups. CA-125 level was more commonly elevated in primary ovarian lesions (87% vs 50%, p=0.018), and with much higher values (1076.5 vs 155.1, p=0.013). CEA level was more commonly elevated in metastatic ovarian lesions (83.3% vs 15.4%, p<0.001), and with higher values (72.4 vs 2.1, p<0.001).

Ovarian metastases were more frequently smooth-margined and cystic with little enhancement. Primary ovarian lesions were more commonly associated with lymphadenopathy and larger volume of ascites. Tumor markers CEA and CA-125 were more frequently elevated in metastatic and primary lesions, respectively. Cancer history was the only variable that increased the odds of metastasis and therefore it is important to always correlate with history of cancer.

Ovarian cancer presents a significant treatment challenge due to its insidious nature and high malignancy. As autophagy is a vital cellular process for maintaining homeostasis, targeting the autophagic pathway has emerged as an avenue for cancer therapy. In the present study, we identify apolipoprotein B100 (ApoB100), a key modulator of lipid metabolism, as a potential prognostic biomarker of ovarian cancer. ApoB100 functioned as a tumor suppressor in ovarian cancer, and the knockdown of ApoB100 promoted ovarian cancer progression in vivo. Moreover, ApoB100 blocked autophagic flux, which was dependent on interfering with the lipid accumulation/endoplasmic reticulum (ER) stress axis. The effects of LFG-500, a novel synthetic flavonoid, on ApoB100 induction were confirmed using proteomics and lipidomics analyses. Herein, LFG-500 induced lipid accumulation and ER stress and subsequently blocked autophagy by upregulating ApoB100. Moreover, data from in vivo experiments further demonstrated that ApoB100, as well as the induction of the lipid/ER stress axis and subsequent blockade of autophagy, were responsible for the anti-tumor effects of LFG-500 on ovarian cancer. Hence, our findings support that ApoB100 is a feasible target of ovarian cancer associated with lipid-regulated autophagy and provide evidence for using LFG-500 for ovarian cancer treatment.

Cancer-associated fibroblasts (CAFs) represent a critical stromal component of metastatic niche and promote metastasis in patients with ovarian cancer (OC). Here, we try to further understand the mechanism by which CAFs-derived exosomes (CAFs-Exo) promoted angiogenesis in OC. We intersected differentially expressed genes in OC cells after CAFs-Exo treatment in the GSE147610 dataset with a list of transcription factors to identify homeobox protein hox-D11 (HOXD11) as a possible cargo of CAFs-Exo. HOXD11 encapsulated by CAFs-Exo enhanced colony formation, migration, and invasion of OC cells. HOXD11 bound to the promoter of fibronectin (FN1) and promoted its transcription. HOXD11 knockdown from CAFs-Exo significantly repressed the VEGF and CD31 protein expression and tube formation, viability, and migration of human umbilical vein endothelial cells (HUVEC) and slowed angiogenesis and tumor growth in mice. Furthermore, we found that overexpression of FN1 increased the expression of angiogenic factors and activity of HUVEC in the presence of HOXD11 knockdown. These results verify the significant contribution of CAFs-Exo to angiogenesis in OC, which could be partially due to the promotion of FN1 mediated by HOXD11.

Ovarian cancer (OC), owing to its substantial heterogeneity and high invasiveness, has historically been devoid of precise, individualized treatment options. This study aimed to establish integrated consensus subtypes of OC using different multiomics integration methodologies.

We integrated five distinct multiomics datasets from multicentric cohorts to identify high-resolution molecular subgroups using a combination of 10 and 101 clustering and machine learning algorithms, respectively, to develop a robust consensus multiomics-related machine learning signature (CMMS).

Two cancer subtypes with prognostic significance were identified using multiomics clustering analysis. 10 essential genes were identified in the CMMS. Patients in the high CMMS group exhibited a poorer prognosis, with a "cold tumor" phenotype and an immunosuppressive state with reduced immune cell infiltration. In contrast, patients in the low CMMS group exhibited a more favorable prognosis, with immune activation and a "hot tumor" phenotype characterized by increased tumor mutation burden, tumor neoantigen burden, PD-L1 expression, and enriched M1 macrophages. Eight independent immunotherapy datasets were validated to further corroborate our findings regarding patients in the low CMMS group who responded better to immunotherapy.

CMMS detection has significant utility in the prognosis of patients at an early stage and identification of potential candidates for immunotherapy.

Ovarian cancer remains low in prevalence but has the highest mortality of all gynecologic malignancies. Population-based screening for ovarian cancer remains a topic of interest in contemporary practice, given that the majority of cancers encountered are high-grade aggressive malignancies, for which favorable survival is encountered in the setting of early-stage disease. This document summarizes a review of the available data from randomized and observational trials that have evaluated the role of imaging for ovarian cancer screening in average-risk and high-risk patients. When considering screening using pelvic ultrasound in average-risk patients, we found insufficient published evidence to recommend ovarian cancer screening. Randomized controlled trials have not demonstrated a mortality benefit in this setting. Screening with pelvic ultrasound may be appropriate for select patients at high risk, although the existing data remain limited as large, randomized trials have not been performed in this setting. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

ObjectivesThis study aimed to explore the expression of eukaryotic translation initiation factor 3 subunit C-like in serous ovarian cancer samples (both paraffin-embedded and fresh samples) and evaluate its clinical value in patients with serous ovarian cancer.MethodsTwenty-five fresh serous ovarian cancer tissues and their paired paratumor tissues were subjected to reverse transcription-quantitative polymerase chain reaction assay to detect eukaryotic translation initiation factor 3 subunit C-like messenger RNA expression. In addition, 135 paraffin-embedded serous ovarian cancer samples and 36 paratumor samples were assessed for eukaryotic translation initiation factor 3 subunit C-like protein expression using immunohistochemistry.ResultsBoth protein and messenger RNA expression levels of eukaryotic translation initiation factor 3 subunit C-like were higher in serous ovarian cancer samples than in paratumor samples, and its high expression was associated with poor overall survival in patients with serous ovarian cancer. In addition, multivariate Cox regression analysis showed that high expression of eukaryotic translation initiation factor 3 subunit C-like was an independent poor prognostic factor for patients with serous ovarian cancer.ConclusionsEukaryotic translation initiation factor 3 subunit C-like is upregulated in serous ovarian cancer samples, and it may be recommended as a useful poor prognostic biomarker in patients with serous ovarian cancer.

This study identifies barriers and facilitators for implementing opportunistic salpingectomy (OS) during non-gynecological abdominal surgeries from a healthcare provider perspective.

From October 2023 to July 2024, a mixed-method study was conducted. The qualitative phase involved semi-structured focus group interviews and individual interviews with specialists in surgery (gynecologists, general surgeons, urologists, and residents) and policymakers to identify barriers and facilitators for implementing OS during non-gynecological surgery. The quantitative phase consisted of a cross-sectional web-based survey assessing the importance of these barriers and facilitators. The study utilized the standardized implementation frameworks to categorize the factors into six domains: innovation, patient, healthcare professional, social setting, organization, and economic and financial context.

In the qualitative phase, 38 healthcare professionals and policymakers identified 38 barriers and 28 facilitators. Barriers were found in all domains and mainly included increased workload, unclear invoicing, and variations in eligible surgeries. Facilitators included the poor prognosis of ovarian cancer, simplicity of OS, and availability of counseling materials. The quantitative survey revealed that 75% of gynecologists, 60% of surgeons, and 61% of urologists supported offering OS during non-gynecological abdominal surgeries. Barriers identified included the ambiguity regarding which patients are eligible for OS, the perceived complication risks of OS, the increased workload as a result of adding OS, and the unclarity around invoicing an OS. Facilitators included the poor prognosis of ovarian cancer, the availability of uniform counseling materials, education on counseling and technical performance of OS, involvement of a gynecologist during the counseling, and clear agreements between the departments within hospitals.

Key barriers to OS implementation in non-gynecological surgeries include unclear invoicing and increased workload, while significant facilitators are the availability of counseling materials and education on counseling and technical performance of OS. Addressing these barriers and leveraging facilitators could enhance OS adoption, potentially reducing ovarian cancer incidence.

New three-dimensional (3D) augmented reality technology represents an opportunity to improve presurgical planning. This study aimed to measure the accuracy of 3D volumetric rendering on augmented reality headsets to predict extent of disease prior to ovarian cancer cytoreductive surgery.

This single-institution prospective study took place from 03/01/2024 to 10/01/2024. Utilizing Medivis 3D augmented reality headsets, investigators reviewed volumetric renderings for patients with suspected advanced ovarian cancer prior to scheduled surgery and filled out a survey predicting presence of disease based on anatomic site. Pathology records were later reviewed to confirm the presence of disease. Statistical analyses included Cohen's kappa coefficient, sensitivity/specificity, and positive/negative predictive value measurements.

We included 15 patients: 9 (60 %) with interval cytoreduction and 6 (40 %) with primary cytoreduction. For procedure, 14 (93 %) had complete gross resection and 1 (7 %) suboptimal cytoreduction (>1 cm of residual disease). Using pathology results as the gold standard for each anatomic site, the 3D headset demonstrated accuracy of 100 % for omentum and pelvic lymph nodes; 93 % for para-aortic lymph nodes, right diaphragm, rectum, and liver; 87 % for small mesentery; and 80 % for small bowel serosa, spleen, and left diaphragm (P > 0.05 for all).

The use of preoperative 3D volumetric rendering on augmented reality headsets to predict the extent of ovarian cancer spread showed high agreement with pathology across all anatomic sites studied. Additional research is needed to assess the potential role of this technology in improving surgical planning and patient outcomes.

Liquid biopsy is a promising approach for early detection of gynecological malignancies. In the PERCEIVE-I study, gynecological Cancer cases (n = 249) and age-matched non-cancer controls (n = 249) are randomly divided into training and test sets at a 1:1 ratio. Data derived from multi-omics assays are obtained including a cell-free DNA methylation panel targeting ≈490 000 CpG sites, a mutation panel comprising 168 genes, and eight tumor protein markers. The results showed that the methylation model outperformed the protein and mutation models, demonstrating higher sensitivity (77.2%) while maintaining similar specificity. The multi-omics model combining methylation and protein markers achieved improved sensitivity (81.9%) with a good specificity (96.9%). The sensitivity varied across different stages, ranging from 66.7% to 100%. The model accurately identified the tissue of origin in 72.1% of cases. The superior performance of the methylation model highlights the potential of integrating multi-omics for non-invasive early detection of gynecological malignancies.