Search Results (378)

Background and Objectives: BRCA1-interacting protein C-terminal helicase 1 (BRIP1) encodes a member of the RecQ DEAH helicase family and interacts with the BRCT repeats of breast cancer type 1 (BRCA1). It also participates in DNA damage repair and tumor suppression; thus, its mutations may be associated with an increased risk of several cancers, including fallopian tube and ovarian cancer. Recent research has explored whether BRIP1 dysregulation also contributes to the development and progression of other malignancies. This study investigated the clinical and prognostic value of BRIP1 in colorectal cancer (CRC). Materials and Methods: We first analyzed The Cancer Genome Atlas (TCGA) dataset to evaluate the prognostic significance of BRIP1 mRNA expression in CRC. BRIP1 expression was subsequently examined in tumor tissues from 60 CRC patients, and its associations with clinicopathological characteristics and clinical outcomes were assessed. Results: In rectal cancer, a higher BRIP1 expression was associated with younger age. In colon cancer, BRIP1 expression was correlated with gender, lymphatic invasion, carcinoembryonic antigen (CEA) level, pathological stage, M stage, N stage, microsatellite instability (MSI) status, and anatomical tumor location. Survival analysis showed that low BRIP1 expression was associated with poorer overall survival in both rectal and colon cancers significantly. In CRC patient tissues, lower BRIP1 expression was further related to elevated CEA levels and unfavorable clinical outcomes. Lower BRIP1 mRNA expression is significantly associated with aggressive clinicopathological features and poor prognosis in CRC. Conclusions: BRIP1 may serve as a promising biomarker for risk stratification and a potential therapeutic target in the management of CRC. Full article

Background: Ovarian cancer (OC) remains one of the most lethal gynecologic malignancies due to its often-late diagnosis and complex molecular heterogeneity. Understanding the metabolic alterations in OC can provide insights into its pathophysiology and potential therapeutic targets. This study aimed to explore serum metabolomic profiles and their correlation with clinical and pathological features in OC patients. Materials and Methods: Thirty serum samples were collected from patients diagnosed with ovarian tumors (OTs) (n = 24 malignant, n = 6 benign) and undergoing treatment at Careggi University Hospital. Additionally, 47 samples were obtained from age-matched healthy female donors. Serum samples underwent processing and analysis using an H-NMR (Nuclear Magnetic Resonance) platform to identify a panel of metabolites. Correlation analysis between the metabolomic data and clinical parameters was performed using R software (v.4.4.0). Results: Differential metabolomic profiling showed a significant upregulation of metabolites associated with the purine salvage pathway (i.e., hypoxanthine and inosine) and the ketone bodies axis (i.e., acetone, 3-hydroxybutyrate, and acetate) in samples from ovarian tumor (OT) patients compared to healthy donors. Within malignant OC samples, metabolomic profiles significantly correlated with BRCA1/2 mutation status (BRCA1/2-mutated vs. wild-type) and homologous recombination deficiency (HRD) status. Conclusions: The analysis revealed significant variation in specific metabolites such as betaine, creatinine, carnitine, glycerol, and mannose; notably, a downregulation of these metabolites was observed in HRD-positive patients. The study identifies significant metabolomic alterations in OC, implicating pathways such as purine salvage and ketone bodies. Intriguingly, consistent variation in specific metabolites across BRCA/HRD phenotypes underscores their potential as OC biomarkers. Further research is needed to validate these findings and explore their prognostic and therapeutic implications. Full article

The ovary, as the primary organ responsible for reproduction and new life, plays a central role in female development, maturation, and health. Neoplasms arising from the ovary and its associated tissues exhibit substantial heterogeneity in their histopathological and molecular profiles, many of which remain poorly understood. This review aims to summarize recent advances in the understanding of genetic alterations underlying ovarian neoplasms and to explore therapeutic strategies informed by molecular biomarkers and tumor microenvironmental factors. A comprehensive literature search was performed, focusing on genomic alterations, biomarker-guided therapies, and tumor microenvironmental modulation in ovarian cancers. Emphasis was placed on studies addressing lipid mediator pathways and their roles in immune regulation and therapeutic response. Based on diagnostic classifications, recurrent alterations in TP53, MYC, PIK3CA, and KRAS are consistently observed across epithelial and germ cell ovarian tumors, whereas non-epithelial subtypes such as sex cord–stromal tumors (SCSTs) and small-cell carcinoma of the ovary, hypercalcemic type (SCCOHT), are predominantly associated with ARID1A and SMARCA4 mutations, respectively. These findings highlight distinct pathogenic mechanisms linked to specific genetic alterations and reveal potential therapeutic vulnerabilities. Moreover, lipid metabolism has been closely implicated in immune surveillance through STING signaling cascades within innate immune cells, suggesting that lipid mediators and their associated genes may represent promising therapeutic targets in ovarian cancers (OCs). Targeting lipid mediators could be particularly effective in relapsed OCs, as modulating innate immune cells within the tumor microenvironment (TME) may enhance immune surveillance and improve antitumor responses. Integrating genetic and microenvironmental insights offers a promising direction for developing more effective and personalized therapeutic strategies in OC. Full article

Background/Objectives: Epithelial ovarian cancer (EOC) is a leading cause of death among forms of gynecologic cancer. Significant causes of mortality include high recurrence rates and the development of resistance to platinum-based chemotherapy. This highlights the need for reliable prognostic biomarkers to improve patient stratification and inform treatment decisions. Claudin-4, a tight junction protein frequently overexpressed in epithelial tumors, has been associated with tumor progression and resistance to chemotherapy. Methods: We retrospectively analyzed 83 patients with EOC who underwent debulking surgery. Claudin-4 expression was assessed by immunohistochemistry and categorized as high or low based on a semi-quantitative scoring system. Survival outcomes were evaluated using Kaplan–Meier analysis and Cox regression. Predictors of platinum resistance were examined using logistic regression. Results: High Claudin-4 expression was observed in 55.4% of cases and was associated with significantly shorter disease-free survival (DFS) (23 vs. 66 months, p = 0.00024) and overall survival (OS) (85 months vs. NR, p = 0.0031). In multivariable analysis, platinum resistance (DFS; HR 4.99, OS; HR 4.27) and high Claudin-4 expression (DFS; HR 2.46, OS; HR 3.59) were independent predictors of poor outcomes. Logistic regression further demonstrated that high Claudin-4 expression and interval debulking surgery were independent predictors of platinum resistance. Conclusions: High Claudin-4 expression was associated with inferior survival and an increased risk of platinum resistance in EOC. Our findings suggest that Claudin-4 may serve as a negative prognostic biomarker and a potential therapeutic target. Future prospective studies are warranted to further elucidate the underlying mechanisms and validate Claudin-4’s clinical utility. Full article

High-grade serous ovarian carcinoma is the most common and aggressive form of ovarian cancer, accounting for over 60% of cases and nearly 75% of deaths, mainly due to late diagnosis and tumor aggressiveness. Standard treatment is platinum-based chemotherapy with paclitaxel, but relapse is frequent. This study aimed to identify prognostic biomarkers for patients with poor survival outcomes after Taxol treatment using bioinformatics analysis. We examined the effects of TGFB2 mRNA expression and other markers on overall survival in serous ovarian cancer using the TCGA database, applying a multivariate Cox model that included interaction terms to identify TGFB2-dependent and independent prognostic markers, and controlling for age and treatment type. Candidate TGFB2-independent prognostic markers from TCGA were further validated using patient data from the KMplotter database. High TGFB2 mRNA expression emerged as a prognostic biomarker for three potential gene targets (TRPV4, STAU2, and HOXC4) associated with improved OS at low levels of gene target expression, we identified four additional markers (CLIC3, ANPEP/LAP1, RIN2, and EMP1) that exhibited a TGFB2-independent negative correlation between mRNA expression and OS across the full spectrum of gene expression values in the ovarian cancer cohort validated using independent dataset from KMplotter, for Taxol-treated ovarian cancer patients. This study proposes a panel of potential prognostic biomarkers for the treatment of ovarian cancer patients, particularly by leveraging TGFB2-dependent mRNA expression as a significant biomarker, alongside four additional TGFB2-independent prognostic markers, for patients undergoing Taxol-based therapies. Future prospective clinical trials will be required to validate these prognostic markers. Full article

Background/Objectives: Achieving complete resection (R0) during secondary cytoreduction (SCR) is a pivotal prognostic factor for patients with platinum-sensitive relapsed ovarian cancer (PSROC). Methods: By integrating single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and functional assays on primary cells, we identified tumor microenvironment (TME) heterogeneity, particularly the presence of distinct subpopulations of cancer-associated fibroblasts (CAFs), as a critical determinant of surgical outcomes for SCR. Results: We characterized a previously unrecognized CAF-C7 subpopulation that was selectively enriched in tumors from non-R0 patients. Mechanistically, CAF-C7 promoted tumor cell migration, suppressed anoikis, and facilitated angiogenesis via the IGF1-IGF1R signaling axis, thereby contributing to multifocal recurrence and reducing the likelihood of complete resection. Importantly, the inhibition of the IGF1-IGF1R pathway effectively attenuated the pro-tumorigenic functions of CAF-C7. Conclusions: These findings uncover a novel cellular driver of unfavorable surgical outcomes in PSROC and suggest promising biomarkers and therapeutic targets for improving patient stratification and treatment in the context of SCR. Full article

Background: Ovarian cancer ascites contributes to the immunosuppressive tumor microenvironment (TME) via macrophage-derived chemokine ligand 23 (CCL23) signaling, T-cell exhaustion, and upregulating pro-inflammatory cytokines. However, the extent to which ascites-derived CCL23 concentrations associate with changes in pro- and anti-inflammatory cytokines and overall patient survival in ovarian cancer patients remains unknown. Methods: CCL23 concentrations and pro-inflammatory cytokines were measured from ascites of stage III and IV epithelial ovarian cancer patients by ELISA and Luminex assays, respectively. Kaplan–Meier survival analysis was performed using patient outcome data from Stanford University Hospital and the Cancer Genome Atlas. The impact of CCL23 peptides on pro-inflammatory cytokine secretion was evaluated in vitro using differentiated THP-1 monocytes. Results: A total of 40 patients were enrolled and CCL23 concentrations were detected in all ascites samples (median = 2.42 ng/mL; range [0.06–6.45]). Reduced survival time corresponded with high CCL23 containing samples (mOS: 3.2 years, [3.9 ng/mL]) versus intermediate (mOS: 6.0 years, [2.5 ng/mL]) or low (mOS: 5.9 years; [1.4 ng/mL]) groups. TGCA analysis of patient outcomes was confirmatory. A significant negative correlation was observed between high CCL23 ascites concentrations versus CXCL10 and soluble PD-1 cytokine levels. High tumor expression of CXCL10 was associated with improved survival (mOS; 5.9 years) versus low CXCL10 expression (mOS; 3.2 years). In vitro, CCL23-stimulated THP-1 macrophages exhibited reduced CXCL10 secretion via STAT-3 activation. Conclusions: High CCL23 concentrations in ovarian cancer ascites reduces CXCL10 secretion from myeloid cells and associates with reduced patient survival. Full article

Ovarian tumors constitute a complex and heterogeneous group of neoplasms, encompassing both benign and highly malignant lesions. Accurate diagnosis and classification of ovarian tumor types are crucial for the personalization of therapeutic strategies and have a significant impact on patient prognosis. This review presents the current state of knowledge regarding both classical and novel biomarkers, with particular emphasis on their diagnostic, predictive, and prognostic value. Traditional markers, such as CA-125 and human epididymis protein 4 (HE4), remain central to clinical diagnostics; however, their limitations highlight the need for more sensitive and specific approaches. Emerging biomarkers, including microRNAs (miRNA), circulating tumor DNA (ctDNA), and advanced panels integrating transcriptomic, proteomic, and genomic data, offer the potential for earlier detection, improved disease monitoring, and assessment of treatment response. Despite these advances, major challenges persist, particularly those associated with the heterogeneity of ovarian tumors, the high costs of testing, lack of standardization, and unequal access to diagnostic methods. Full article

Ovarian cancer is a highly aggressive disease with a poor prognosis, largely due to challenges in early detection. Traditional screening methods, including transvaginal ultrasound (TVS) and CA125 testing, have notable limitations in detecting early-stage disease and are not advised for widespread use. This article examines emerging early detection technologies, such as novel biomarkers, circulating DNA, PCR assays from Pap swabs, autoantibodies, microRNAs, and advanced imaging techniques. Future advancements in therapeutic methods may enhance survival outcomes linked to early detection. While general population screening remains unendorsed, targeted screening might be valuable for high-risk groups, such as those with Lynch syndrome, but should not replace risk-reducing surgeries. Developing comprehensive screening guidelines for high-risk individuals is essential for improving early detection and survival rates in ovarian cancer. Full article

Background/Objectives: Therapeutic resistance remains a major obstacle in breast cancer management, particularly among estrogen receptor-positive (ERα⁺) tumors that initially respond to endocrine therapy such as tamoxifen. Type XI collagen (COL11A1), a minor fibrillar collagen secreted by cancer-associated fibroblasts, has recently emerged as a stromal biomarker linked to tumor progression, immune modulation, and poor prognosis in several solid malignancies. Methods: We conducted a narrative review of the literature indexed in PubMed, Scopus, and Web of Science between 2011 and 2025, including original research, reviews, and clinical studies addressing COL11A1 expression and function in breast cancer. Mechanistic studies in other cancer types (ovarian, pancreatic, lung) were also evaluated when relevant to breast cancer biology. Results: Across multiple cancer types, COL11A1 overexpression correlates with stromal remodeling, epithelial–mesenchymal transition, and resistance to both hormone therapy and chemotherapy. In breast cancer, emerging data suggest a potential prognostic role and possible involvement in shaping the immune microenvironment. Nevertheless, most evidence derives from retrospective or preclinical studies, and clinical validation remains limited. Conclusions: COL11A1 represents a promising, though still exploratory, biomarker of therapeutic resistance and immune modulation in breast cancer. Future prospective and subtype-specific studies are needed to clarify its diagnostic and therapeutic value and to determine whether its inclusion in immunohistochemical panels could enhance patient stratification and guide personalized treatment. Full article

Ovarian cancer stem cells (OCSCs) possess stemness; differentiation capacity; and tolerance to oxidative, metabolic, and therapeutic stress, driving recurrence and chemoresistance. Emerging evidence highlights a synergistic interplay between redox homeostasis and amino acid metabolism in maintaining stemness and treatment resistance. This review integrates redox regulation, amino acid metabolic reprogramming, and tumor microenvironment (TME) signals into a unified “redox–amino acid–TME” framework. OCSCs balance signal transduction and antioxidant defense by fine-tuning reactive oxygen species (ROS) levels. Glutamine, serine/glycine, and sulfur amino acid metabolism collectively generate NADPH and glutathione, sustaining the GPX4/TRX antioxidant systems and suppressing ferroptosis. Branched-chain amino acid (BCAA)–mTOR and tryptophan (Trp)–aryl hydrocarbon receptor (AhR) axes couple amino acid sensing to redox signaling, stabilizing the stem-like phenotype. Under TME stress, including hypoxia, acidity, and nutrient competition, exosomes and stromal components reinforce stemness and immune evasion through metabolic and redox crosstalk. Therapeutically, targeting glutamine metabolism (ASCT2/GLS), serine biosynthesis (PHGDH/SHMT), or antioxidant defenses (xCT/GPX4) disrupts reducing power, increases oxidative stress, and enhances the efficacy of chemotherapy, PARP inhibition, and immunotherapy. Biomarkers such as xCT/GPX4 expression, PHGDH levels, Nrf2 activity, and GSH/NADPH ratios may guide patient stratification and response prediction. Overall, understanding the redox–amino acid metabolic network provides a mechanistic basis and translational opportunities for precision metabolic therapies in ovarian cancer. Full article

Ovarian cancer is the gynecologic malignancy that bears the highest mortality rate in the Western world. This is attributed to late diagnosis and limited therapeutic progress. Recent advances in molecular oncology have highlighted the pivotal role of epigenetic modifications—including DNA methylation, histone modifications, non-coding RNAs, chromatin remodeling, and RNA methylation—in ovarian cancer development, progression, and treatment resistance. DNA methylation patterns affect key tumor suppressors and oncogenes, while histone modifications alter chromatin accessibility, influencing gene expression. Chromatin remodeling complexes, particularly the SWI/SNF complex, are frequently mutated in specific ovarian cancer subtypes, which is central in shaping their biological behavior. Non-coding RNAs, including microRNAs and long non-coding RNAs, further regulate tumor cell behavior and the immunosuppressive tumor microenvironment. Epigenetic profiles vary among histological subtypes and hold promise for biomarker development, early detection, prognosis, and therapeutic monitoring. Liquid biopsy approaches leveraging circulating tumor DNA methylation show diagnostic potential superior to conventional markers. Moreover, targeting epigenetic regulators—such as DNMT and HDAC inhibitors, EZH2 antagonists, and RNA-modifying enzymes—offers novel avenues for treatment, particularly in reversing chemoresistance and sensitizing tumors to immunotherapy. While promising, these strategies require further validation through clinical research to translate into effective clinical interventions. This review aims to summarize the current literature and highlights potential applications of epigenetic manipulation in day-to-day practice. Full article

The FAM171A2 gene encodes a transmembrane protein that is not well characterized but is implicated in signaling, vesicle trafficking, and interactions with the extracellular matrix. Its specific role in gynecologic malignancies has yet to be defined. To our knowledge, this is the first systematic study to comprehensively assess FAM171A2 expression, clinical relevance, and molecular network interactions in gynecologic malignancies. We employed an integrative approach utilizing multi-platform transcriptomic and proteomic resources—GEPIA2, TNMplot, TIMER2, UALCAN, KM-plotter, Human Protein Atlas (HPA), Gene Expression Omnibus (GEO), STRING, TargetScan, and ENCORI—to comprehensively profile FAM171A2 expression, its clinicopathologic correlations, survival associations, predicted interaction networks, and post-transcriptional regulation in ovarian cancer (OV) and uterine corpus endometrial carcinoma (UCEC). Immunohistochemical analysis from the HPA indicated low or undetectable levels of the FAM171A2 protein in OV and UCEC. In contrast, RNA sequencing analyses demonstrated upregulated mRNA expression in OV and a modest, non-significant increase in UCEC compared to normal tissues. Pan-cancer screening using TNMplot and TIMER2 revealed elevated expression in gynecologic tumors relative to most other cancer types. In OV, UALCAN analysis identified associations with demographic and molecular characteristics, such as increased expression in TP53-mutant tumors, while trends related to stage and grade were minimal. Similarly, stratifications in UCEC suggested modulation by race, body mass index (BMI), and menopausal status rather than stage. Survival analyses using KM-plotter showed no significant association with overall survival in either type of cancer. TargetScan predicted 211 microRNAs potentially targeting FAM171A2, and ENCORI correlations supported tumor-type-specific post-transcriptional regulation: in OV, negative correlations were observed with miR-15b-5p, miR-16-5p, and miR-497-5p, along with long non-coding RNA (lncRNA) effects, including positive correlations with BACE1-AS and negative correlations with PVT1 and UCA1. In UCEC, significant negative correlations were found with LINC00582, LINC-ROR, MEG3, NEAT1, and SNHG12. STRING network analysis suggested two modules associated with FAM171A2: a neuronal/synaptic cluster, exemplified by NPTX1, and an immune/transcriptional cluster, exemplified by ZNF696. Validation using the GEO showed mixed results: two UCEC datasets were non-significant, whereas one OV cohort (GSE36368) exhibited higher tumor expression. FAM171A2 demonstrates context-dependent expressions that are modulated post-transcriptionally in gynecologic cancers. While it is not independently prognostic, it may serve as a molecular hub at the intersection of neuronal and immune pathways, warranting further mechanistic investigations and exploration as a panel-based biomarker. Full article

Background: Ovarian cancer (OC) is the second most common gynecologic malignancy in the United States and remains the leading cause of death among cancers of the female reproductive system. Alarmingly, mortality rates have risen disproportionately among women of African ancestry compared to those of European or Asian descent. Identifying microRNA (miRNA) signatures that contribute to these disparities may enhance prognostic accuracy and inform personalized therapeutic strategies. Methods: In this study, we identified prognostic markers of overall survival in serous ovarian cancer (SOC) using data from The Cancer Genome Atlas (TCGA) and the Human Protein Atlas. Integrative bioinformatic analyses revealed three key prognostic genes—TIMP3 (Tissue Inhibitor of Metalloproteinases-3), BRAF (v-raf murine sarcoma viral oncogene homolog B), and ITGB1 (Integrin Beta-1)—as critical molecular determinants associated with survival in patients with SOC. Candidate miRNAs regulating these genes were predicted using TargetScanHuman v8.0, identifying a core regulatory set comprising miR-192, miR-30d, miR-16-5p, miR-143-3p, and miR-20a-5p. To validate their clinical relevance, formalin-fixed, paraffin-embedded (FFPE) and fresh SOC tumor samples were obtained from African American and Caucasian patients who underwent surgery at Loma Linda University (LLU) between 2010 and 2023. Results and Discussion: Among all these, ITGB1 (p = 0.00033), TIMP3 (p = 0.0035), and BRAF (p = 0.026) emerged as statistically significant predictors. Following total RNA extraction, cDNA synthesis, and quantitative reverse transcription PCR (qRT-PCR), the expression levels of these miRNAs and their target genes were quantified. In the LLU cohort, ITGB1 and TIMP3 were significantly upregulated in African American patients compared to Caucasian patients (p < 0.01 and p < 0.02, respectively). Among the miRNAs, miR-192-5p was particularly noteworthy, showing marginally differential expression in LLU samples (p = 0.0712) but strong statistical significance in the TCGA cohort (p = 0.00013), where elevated expression correlated with poorer overall survival (p = 0.021). Pathway enrichment and gene ontology analyses (miRTargetLink2.0, Enrichr) revealed interconnected regulatory networks linking miR-192, miR-16-5p, miR-143-3p, and miR-20a-5p to ITGB1; miR-143-3p/miR-145-5p to BRAF; and miR-16-5p and miR-30c/d to TIMP3. Conclusions: Collectively, these findings identify distinct miRNA–mRNA regulatory signatures—particularly the miR-192-5p–ITGB1/TIMP3 axis—as potential clinically relevant biomarkers that may contribute to racial disparities and disease progression in ovarian cancer. Full article

Background/Objectives: Tubo-ovarian high-grade serous carcinoma (HGSC) is a highly lethal malignancy, usually diagnosed at an advanced stage due to the lack of early symptoms and biomarkers. Contraceptive hormone use is associated with a reduced risk of HGSC, but the relative contributions of natural versus synthetic progestins, and their interaction with estrogens, are poorly understood. Methods: We evaluated the chemo-preventive efficacy of a synthetic progestin medroxyprogesterone acetate (MPA), progesterone (P4), and combined 17β-estradiol-progesterone (E2 + P4) in a well-characterized genetically engineered mouse model (GEMM) of oviductal HGSC based on the conditional inactivation of one or both alleles of the Brca1, Trp53, Rb1, and Nf1 tumor suppressor genes (BPRN-het and BPRN-homo mice, respectively). Mice received hormones or placebo via slow-release pellets implanted subcutaneously. After induction of tumor formation, the mice were monitored for tumor development, progression, and survival. Tumor incidence was assessed histologically, and hormone effects were further explored via RNA-seq analysis of oviductal tissues. Results: MPA significantly reduced HGSC incidence and delayed tumor progression compared to the placebo, P4, and P4 + E2 in both BPRN-homo and BPRN-het mice, with up to 78% tumor-free survival in the MPA-treated BPRN-het cohort. P4 monotherapy did not provide significant protection vs. the placebo, but the effects of P4 could have been impacted by a failure to achieve sustained release of the hormone beyond 4–8 weeks. The E2 + P4 combination accelerated tumorigenesis and reduced survival (p < 0.0001 in BPRN-homo and p = 0.0004 in BPRN-het mice). MPA did not affect tumorigenesis in a colon cancer GEMM, or the growth of mouse HGSC-derived cells in vivo, suggesting the role of MPA in the early stages of HGSC development. Gene expression analyses showed that P4 and MPA downregulated cholesterol homeostasis, early and late estrogen response, and epithelial–mesenchymal transition pathways, though only MPA afforded tumor protection. Conclusions: These findings demonstrate that a synthetic progestin, specifically MPA, confers robust protection against HGSC development, while a combination including E2 (E2 + P4) increases risk. This work also illustrates how HGSC GEMMs can be used to compare the chemo-preventive effects of various synthetic progestins on HGSC development in order to prioritize the most effective ones for use in preventing HGSC in both general and high-risk populations. Full article