This study aimed to investigate the role of FAM172A in epithelial ovarian cancer (EOC), a highly lethal gynecological malignancy often diagnosed at late stages with limited treatment options. FAM172A expression was evaluated in EOC and normal ovarian tissues using western blotting and immunohistochemistry, and its association with patient prognosis, treatment response, and CA125 levels was assessed by multivariate regression analysis. Functional assays were performed to examine the effects of FAM172A on EOC cell proliferation, migration, and invasion. In vivo models were used to evaluate the influence of FAM172A on tumor growth, metastasis, and chemosensitivity. The underlying mechanism was explored by modulating the PI3K-Akt pathway with pharmacological inhibitors and activators. FAM172A was significantly upregulated in EOC tissues, and its elevated expression correlated with poor prognosis, chemotherapy resistance, and increased CA125 levels. Multivariate analysis identified FAM172A expression, platinum sensitivity, and CA125 as independent prognostic factors. In vitro, FAM172A promoted malignant behavior and conferred resistance to cisplatin. In vivo, knockdown of FAM172A suppressed tumor progression and enhanced the efficacy of cisplatin. Mechanistically, FAM172A exerted its effects through regulation of the PI3K-Akt pathway, and modulation of PI3K signaling rescued FAM172A-induced phenotypic changes. These findings highlight FAM172A as a critical promoter of EOC progression, associated with aggressive tumor characteristics and treatment failure. By activating the PI3K-Akt pathway, FAM172A represents a promising therapeutic target for EOC, potentially offering new strategies to improve patient outcomes, particularly in overcoming chemoresistance.

Cytoplasmic SIRT1 enhances the stemness of polyploid giant cancer cells by promoting β-catenin protein stability and nuclear accumulation in ovarian carcinoma upon neoadjuvant chemotherapy.

Timing matters: Surgery-to-chemotherapy interval and outcomes in ovarian cancer.

A prospective comparison of resectability scores to enhance preoperative decision-making in the primary management of advanced ovarian cancer: a Memorial Sloan Kettering Cancer Center Team Ovary study.

Quantifying opportunities to reduce high grade serous ovarian cancer via opportunistic salpingectomy.

Letrozole plus anlotinib as a chemotherapy-free regimen for ER-positive platinum-resistant recurrent epithelial ovarian cancer patients following second-line platinum-based chemotherapy failure: A prospective, single-arm, open-label, phase II study.

Construction of a circRNA-miRNA-mRNA ceRNA regulatory network identifies RNAs and genes linked to human ovarian clear cell carcinoma.

ABSTRACT Plantago loeflingii L. (Plantaginaceae) is traditionally used for wound healing and tumor treatment, yet its cellular effects remain unexplored. This study provides the first integrated evaluation of its essential oil (PLA‐EO), including chemical composition, cytotoxicity, mechanistic assays, and molecular docking. Hydrodistillation followed by GC–MS/GC–FID identified 53 constituents (98.33%), dominated by linalool (23.81%), palmitic acid (15.34%), limonene (10.54%), thymol (8.51%), and α‐terpineol (5.23%). PLA‐EO selectively inhibited ovarian adenocarcinoma BG‐1 cells (IC 50 = 5.67 ± 0.6 µg/mL) while sparing MCF7, A549, and normal cells. Mechanistic assays revealed ER stress‐mediated apoptosis, as indicated by ER expansion, GRP78 upregulation, Ca 2 + overload, and caspase‐3 activation. To explore upstream triggers, molecular docking was performed against the EGFR kinase domain (PDB: 3W2S). The docking protocol was validated by redocking (RMSD = 0.98 Å), and erlotinib (−8.96 kcal/mol) reproduced known interactions with ASP855, ALA859, and PHE723. Palmitic acid (−9.05 kcal/mol) interacted with ARG836 via hydrogen bonding and hydrophobic contacts, while linalool (−7.17 kcal/mol) engaged ASP855 and PHE723. These interactions suggest possible EGFR modulation, though activity likely reflects synergistic contributions from multiple PLA‐EO components. In conclusion, PLA‐EO exhibits selective cytotoxicity in ovarian cancer cells via ER stress pathways, supported by in silico evidence of EGFR targeting. The combined phytochemical, cellular, and docking results highlight P. loeflingii as a promising source of bioactive essential oils, warranting further in vivo validation.

Tertiary lymphoid structures (TLS) have become the focus of antitumor immunity. However, the prognostic significance of TLS in epithelial ovarian cancer (EOC) treated with primary debulking surgery (PDS) or interval debulking surgery (IDS) remains unclear. Therefore, we aimed to examine TLS in tumor tissues collected during PDS and IDS for patients with EOC to evaluate its prognostic significance. We examined TLS in EOC tumor tissues obtained during PDS or IDS from patients treated between 2017 and 2020 at the National Cancer Center Hospital East, Kashiwa, Japan. The association of tumor-infiltrating lymphocyte frequency, TLS presence, and programmed death-ligand 1 (PD-L1) expression with progression-free (PFS) and overall (OS) survival, and the association between TLS and PD-L1 expression were analyzed. Overall, 25 specimens (15 from PDS and 10 from IDS) were analyzed. The presence of TLS was associated with a significantly longer OS (median: 32.3 vs. 21.3 months, p=0.0455) in patients who underwent PDS but not in patients who underwent IDS (median: could not be calculated, p=0.9678). No association was identified between TLS and PFS in patients with PDS or with IDS (median: 31.1 vs. 17.3 months, p=0.3970; median: 28.7 vs. 16.3 months for median without TLS, p=0.1653). However, TLS was positively correlated with PD-L1 positivity (p=0.0094). The prognostic impact of TLS, specifically in pre-chemotherapy specimens, and a positive association between TLS and PD-L1 indicate the potential of TLS as a meaningful biomarker for understanding antitumor immunity and developing immunotherapy for EOC.

Circulating plasma gelsolin and MRI-based radiomics as biomarkers of platinum resistance in epithelial ovarian cancer: building a multiparameteric prediction algorithm.

Integrin alpha-3 (ITGA3) has been implicated in tumor metastasis in various cancers, but its role in epithelial ovarian cancer (EOC)-associated liver metastasis (LM) remains unclear. This study aimed to investigate its role in LM in primary EOC patients. It was a retrospective study with a sample size of n = 235 receiving surgical resection at Puren Hospital Affiliated to Wuhan University of Science and Technology between January 2020 and December 2021, including 98 LM (LM group) and 137 non-LM cases (N-LM group). ITGA3 expression was assessed by immunohistochemistry. ROC curves were used for predictive performance analysis, Kaplan-Meier curves for survival analysis, and Cox regression analysis for identification of risk factors. Markedly elevated ITGA3 expression in tumor tissues was found in the LM group (P < 0.001), which demonstrated strong predictive value for LM in EOC patients (area under the curve (AUC) = 0.881, sensitivity = 70.41%, specificity = 87.59%, P < 0.001), and strongly correlated with tumor size and postoperative residual lesions (both P < 0.05). Compared with the L-ITGA3 group, the H-ITGA3 group had a higher incidence of postoperative LM (P < 0.001) and showed a left-shifted curve in Kaplan-Meier analysis (P < 0.001). ITGA3 expression in tumor tissues (HR = 5.977), tumor grade (HR = 1.441), and postoperative residual lesions (HR = 1.697) were identified as independent risk factors for postoperative LM. ITGA3 expression in tumor tissue significantly aids in predicting LM in EOC patients and is independently and closely related to adverse clinicopathological outcomes.

Stromal Tumor infiltrating lymphocytes (sTILs) as a prognostic biomarker in Ovarian Cancer After Neoadjuvant chemotherapy.

Chemotherapy-induced enrichment of cancer stem cells (CSCs) is a key mechanism underlying acquired chemoresistance and recurrence of epithelial ovarian cancer (OC). Although chemotherapy may enrich CSCs through selection or by inducing dedifferentiation, the dynamic changes in the tumor niche and their impact on CSCs during chemotherapy remain unclear. In this study, single-cell sequencing and multiplex immunohistochemical analysis are used to define microenvironmental changes, and a post-chemotherapy increase in efferocytotic macrophages that phagocytosed chemotherapy-induced apoptotic tumor cells is identified. Efferocytotic macrophages are associated with poor prognosis and CSCs in OC. Their conditioned medium facilitates OC stemness in vitro. Meanwhile, targeting efferocytosis suppresses CSC enrichment, chemoresistance, and regrowth in vivo. Mechanistically, it is demonstrated that enhanced expression of ODC1 driven by efferocytosis increases polyamine flux, particularly putrescine, by integrating metabolomics and transcriptomics. The increase in putrescine content leads to the SPP1 and OPN overexpression in macrophages, conferring cancer stemness to OC cells through the OPN-CD44 axis. Treatment with an ODC1 selector inhibitor mitigates CSC enrichment, sensitizes tumors to cisplatin, and restricts tumor regrowth. Together, the study shows that efferocytosis and associated polyamine metabolic reprogramming support the chemotherapy-induced enrichment of CSCs, providing new targets for addressing chemoresistance and recurrence of OC.

Neoadjuvant chemotherapy followed by interval surgery versus primary debulking surgery in FIGO stage III-IV epithelial ovarian cancer: A systematic review and meta-analysis.

Abstract BACKGROUND Paraneoplastic cerebellar degeneration (PCD) is a rare but debilitating autoimmune neurological syndrome often associated with gynecological malignancies, particularly ovarian cancer. PCD may precede the diagnosis of the underlying tumor, and its early recognition is crucial to improving patient outcomes. METHODS We present a case of a 61-year-old woman from Nepal who developed progressive slurred speech and unsteady gait. Initial neurological work-up, cerebrospinal fluid analysis, and serum biomarkers were inconclusive for metastasis or infection. Further investigations, including imaging, histopathology, and immunohistochemistry, were conducted. RESULTS The patient was found to have elevated CA-125 and a strongly positive anti-Yo antibody. Imaging revealed recurrent pelvic masses with metastases. Biopsy confirmed metastatic ovarian adenocarcinoma. Brain MRI later showed cerebellar atrophy and T2/FLAIR hyperintensities. The patient was diagnosed with paraneoplastic cerebellar degeneration secondary to metastatic ovarian carcinoma. CONCLUSION This case underscores the significance of considering paraneoplastic syndromes in patients with unexplained cerebellar symptoms. Timely evaluation and recognition of PCD can facilitate early cancer detection, allowing for earlier intervention and potentially limiting irreversible neurological damage.

Chronic inflammation and inflammatory-related exposures have been implicated in epithelial ovarian cancer (EOC) prognosis. However, no studies have evaluated whether analgesic medication use impacts survival in Black women with EOC, an understudied population with poor survival. Leveraging data from the African American Cancer Epidemiology Study, we examined the association of pre-diagnostic analgesic medication use (aspirin, non-aspirin non-steroidal anti-inflammatory drugs [naNSAIDs], and acetaminophen) with survival among self-identified Black women diagnosed with EOC (N = 541) using multivariable Cox proportional hazards regression. Stratified analyses were conducted by comorbidities and histotype. Acetaminophen use was associated with a higher risk of mortality overall (HR = 1.40; 95% CI = 1.00-1.97) and for frequent and chronic use (≥30 days per month: HR = 1.62; 95% CI = 1.12-2.34; >5 years: HR = 1.57; 95% CI = 1.03-2.39). These associations were more pronounced among women with high-grade serous carcinoma (HGSC)/carcinosarcoma and those with comorbidities. Among women with comorbidities, naNSAID use was associated with a decreased risk of mortality (HR = 0.71; 95% CI = 0.51-0.99), but no association was observed among women without comorbidities (HR = 0.99; 95% CI = 0.56-1.75). No associations with survival were observed for aspirin. Chronic use of acetaminophen negatively impacted survival among Black women with EOC, while naNSAID use conferred a survival advantage only among women with comorbidities.

First-line maintenance therapy with poly(adenosine diphosphate-ribose) polymerase inhibitors (PARP inhibitors) after platinum-based chemotherapy improves progression-free survival (PFS) in advanced epithelial ovarian cancer (EOC), particularly in patients with BRCA-variant or homologous recombination-deficient tumors. However, overall survival (OS) benefits remain uncertain, and toxic effect profiles emphasize the need for optimized patient and agent selection. To evaluate the efficacy and safety of first-line PARP inhibitor maintenance therapy compared with chemotherapy alone in advanced-stage EOC, with subgroup analyses by BRCA and HRD status, up-front or interval surgery, chemotherapy response, and residual disease. Medline, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from database inception to August 19, 2024. Randomized clinical trials and prospective 2-arm studies evaluating PARP inhibitor maintenance therapy in patients with advanced-stage EOC responding to first-line platinum-based chemotherapy were included. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline was followed in reporting this study. Data were independently extracted by 2 reviewers. Random-effects models were used for meta-analysis. Risk of bias was assessed with Cochrane risk of bias and certainty of evidence with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Primary outcomes were PFS and OS; secondary outcomes included high-grade adverse events. A total of 7 randomized clinical trials with 4013 patients with advanced-stage epithelial ovarian cancer responding to first-line platinum-based chemotherapy were included. PARP inhibitor maintenance was associated with improved PFS in the overall population (hazard ratio [HR], 0.57; 95% CI, 0.46-0.70; high certainty) and in all molecular subgroups except the homologous recombination proficient group (BRCA variant: HR, 0.40; 95% CI, 0.35-0.45; BRCA wild type: HR, 0.62; 95% CI, 0.44-0.86; homologous recombination deficient: HR, 0.44; 95% CI, 0.39-0.50; all high certainty). PFS benefits were consistent across surgical timing, chemotherapy responses, and residual disease; for example, surgical timing had HRs of 0.51 (95% CI, 0.31-0.84) for neoadjuvant chemotherapy and 0.54 (95% CI, 0.36-0.81) for primary cytoreductive surgery (all high certainty). No molecular subgroup showed a statistically significant OS improvement (high to low certainty). High-grade adverse events were more common in the PARP inhibitor group (HR, 2.40; 95% CI, 1.16-4.93; high certainty). Observed treatment efficacy and toxic effects varied across PARP inhibitor regimens; for example, the risk ratio for any recurrence or death in the overall study group ranged from 0.53 (95% CI, 0.40-0.70) for senaparib to 0.83 (95% CI, 0.68-1.00) for olaparib, while the risk ratio for high-grade adverse events ranged from 1.15 (95% CI, 0.64-2.06) for veliparib to 4.73 (95% CI, 2.77-8.07) for niraparib. In this study, no subgroup showed an association between first-line PARP inhibitor maintenance therapy in advanced-stage EOC and improved OS, and findings suggest that the consistency of associated PFS benefits may vary, particularly in homologous recombination proficient and BRCA wild type tumors. Variability in efficacy and toxic effects across subgroups and PARP inhibitor regimens underscores the importance of individualized treatment decisions.

Artificial intelligence diagnostic tools show promise for improving histotype classification in epithelial ovarian cancer but face challenges due to slide variability across institutions. To address this domain shift, the adversarial Fourier-based domain adaptation (AIDA) model was developed. This retrospective study evaluates AIDA's performance in classifying the 5 major ovarian cancer subtypes using an independent cohort. Surgically treated patients diagnosed with clear cell (CCC), endometrioid (EC), high-grade serous (HGSC), low-grade serous (LGSC), or mucinous (MC) ovarian cancer at Amsterdam University Medical Center (1985-2022) were included in the study. The deep learning method AIDA, trained on data from Vancouver General Hospital, was applied to all cases. Final histotype predictions were made through majority voting across 15 independently trained models. For misclassified cases, up to 3 additional slides were scanned, and the AIDA model was retrained. Classification was then assessed using single-slide and majority voting approaches. The AIDA algorithm achieved an overall balanced accuracy of 79.7% across all histotypes. Accuracy was highest for CCC (90.9%) and LGSC (89.8%), and lowest for EC (62.4%). Common misclassifications included MC as EC and EC as HGSC or LGSC. Retraining with additional slides improved balanced accuracy to 85.8% based on single-slide voting and 82.6% based on majority voting. This study highlights the future potential of the AIDA model in classifying epithelial ovarian cancer histotypes. With further refinement to improve performance on more challenging cases, the model could enhance diagnostic accuracy in clinical practice.

Epithelial ovarian cancer (EOC) is an aggressive malignancy with limited therapeutic options. Poly(ADP-ribose) polymerase inhibitors (PARPi) have shown remarkable efficacy, especially in BRCA-mutant patients, and are approved as maintenance therapy to prevent recurrence after initial response to chemotherapy. However, the development of PARPi resistance poses a major clinical challenge. This study utilized a whole-genome CRISPR-Cas9 genetic screening to identify genes associated with PARPi sensitivity upon knockout. Based on the screening and validated through further experiments, we confirmed that CLK1 knockdown is synthetically lethal with PARPi in ovarian cancer. The combination of the PARPi Olaparib and CLK1 inhibitor TG003 exhibited potent anti-proliferative effects both in vitro and in vivo. Mechanistically, CLK1 inhibition downregulated the functional ERCC1-202 isoform, resulting in enhanced DNA damage and apoptosis. Our findings reveal a novel mechanism underlying PARPi sensitivity and suggest that targeting CLK1 in combination with PARPi may represent a promising therapeutic strategy for PARPi-resistant ovarian cancer.

Objective: To compare the diagnostic performance of an exosomal ovarian cancer assay (chemiluminescence) with serum CA125 for epithelial ovarian cancer (EOC), focusing on sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Methodology: This retrospective study included 200 patients from the Department of Obstetrics and Gynecology, Hospital of 82nd Group Army PLA (June 2023 to December 2024). Participants were divided into a control group (n = 150, including healthy individuals, patients with pelvic inflammatory disease, and other tumors) and an EOC group (n = 50, confirmed by pathology). Serum samples were analyzed using the exosomal kit and CA125. Agreement metrics (PPA, NPA, OPA) with 95% CIs and Kappa consistency were calculated. Results: There were significant differences in age distribution and menopausal status between the two groups (P&lt;0.05), with marked differences also found in serum HE4, serum CA125, and OCS values between the two groups (P&lt;0.05). The exosomal assay showed a sensitivity of 74.0%, specificity of 99.3%, PPV of 97.4%, and NPV of 92.0%, outperforming CA125 (sensitivity 40.0%, specificity 97.3%, PPV 83.3%, NPV 83.0%). Kappa analysis indicated good agreement between methods (K = 0.797, P &lt; 0.01). Conclusion: The exosomal ovarian cancer diagnostic kit exhibits superior sensitivity and specificity compared to CA125, suggesting strong potential as a complementary tool for early EOC detection.