Ovarian cancer (OC) is the fifth leading cause of women’s death from cancers. The high mortality rate is attributed to the late presence of the disease and the lack of modern diagnostic tools, including molecular biomarkers. Moreover, OC is a highly heterogeneous disease, which contributes to early treatment failure. Thus, exploring OC molecular mechanisms could significantly enhance our understanding of the disease and provide new treatment options. Chromatin remodeling complexes (CRCs) are ATP-dependent molecular machines responsible for chromatin reorganization and involved in many DNA-related processes, including transcriptional regulation, replication, and reparation. Dysregulation of chromatin remodeling machinery may be related to cancer development and chemoresistance in OC. Some forms of OC and other gynecologic diseases have been associated with mutations in specific CRC genes. Most notably, ARID1A in endometriosis-related OC, SMARCA4, and SMARCB1 in hypercalcemic type small cell ovarian carcinoma (SCCOHT), ACTL6A, CHRAC1, RSF1 amplification in high-grade serous OC. Here we review the available literature on CRCs’ involvement in OC to improve our understanding of its development and investigate CRCs as possible biomarkers and treatment targets for OC.

Background: Type II ovarian cancer (OC) is generally diagnosed at an advanced stage, translating into a poor survival rate. Current screening methods for OC have failed to demonstrate a reduction in mortality. The uterine lavage technique has been used to detect tumor-specific TP53 mutations from cells presumably shed from high-grade serous ovarian cancer (HGSOC). We aimed to pilot whether the detection of TP53 mutation in uterine cavity lavage can be used as a diagnostic method for HGSOC using an expanded gene panel. Methods: In this study 90, uterine lavage and 46 paired biopsy samples were analyzed using next-generation sequencing (NGS) targeting TP53 as well as five additional OC-related genes: BRCA1, BRCA2, PI3KCA, PTEN, and KRAS. Results: Uterine lavage was successfully applied to all patients, and 56 mutations were detected overall. TP53 mutations were detected in 27% (10/37) of cases of type HGSOC; BRCA1 and BRCA2 mutations were also frequent in this group (46%; 17/37). Overall concordance between tissue and liquid biopsy samples was 65.2%. Conclusion: Uterine lavage TP53 mutations in combination with other biomarkers could be a useful tool for the detection of lowly invasive HGSOC.

New molecular biomarkers that could have an independent prognostic value in endometrial cancer are currently under investigation. Recently, it was suggested that genetic changes in the Notch signaling pathway could be associated with the development of endometrial carcinoma. This study aimed to determine the expression of the Notch signaling pathway components in tumour and adjacent normal uterine tissue and to evaluate their importance for the survival of uterine cancer patients. The present study was performed on uterine body samples collected from 109 patients and paired adjacent noncancerous endometrial tissue samples. KaplanMeier curves and Cox regression were used for survival analyses. Expression alterations of NOTCH2, NOTCH3, NOTCH4, JAG2, and HES1 were evaluated as independent and significant prognostic factors for uterine cancer patients.

This study aimed to evaluate the diagnostic potential of soluble Programmed Death Ligand 1 (sPD-L1) and Programmed Death 1 (sPD-1) molecules in plasma, along with urinary mRNA biomarkers—Prostate-Specific Membrane Antigen (PSMA), Prostate Cancer Antigen 3 (PCA3), and androgen receptor (AR) genes—for identifying clinically significant prostate cancer (PCa), defined as pathological stage 3. In a cohort of 68 PCa patients, sPD-L1 and sPD-1 levels were quantified using ELISA, while mRNA transcripts were measured by RT-qPCR. Results highlight the potential of integrating these liquid-based biomarkers. In particular, the combination of sPD-L1, sPD-1, and AR demonstrated the most significant improvement in diagnostic performance, increasing the area under the curve (AUC) from 0.65 to 0.81 and sensitivity from 60% to 88%, compared to AR alone. PSMA demonstrated an AUC of 0.82 and a specificity of 52.8%, which improved to an AUC of 0.85 and a specificity of 94.4% with the inclusion of sPD-L1 and sPD-1. Similarly, PCA3 achieved an AUC of 0.75 and a specificity of 53.8%, increasing to an AUC of 0.78 and a specificity of 76.9% when combined with these biomarkers. Incorporating sPD-L1 into a three-gene panel further elevated the AUC from 0.74 to 0.94. These findings underscore the value of multimodal liquid-based diagnostic panels in improving the management of clinically significant PCa.

(1) Background: DNA damage response (DDR) pathway gene mutations are detectable in a significant number of patients with metastatic castration-resistant prostate cancer (mCRPC). The study aimed at identification of germline and/or somatic DDR mutations in blood and urine samples from patients with mCRPC for correlation with responses to entire sequence of systemic treatment and survival outcomes. (2) Methods: DDR gene mutations were assessed prospectively in DNA samples from leukocytes and urine sediments from 149 mCRPC patients using five-gene panel targeted sequencing. The impact of DDR status on progression-free survival, as well as treatment-specific and overall survival, was evaluated using Kaplan–Meier curves and Cox regression. (3) Results: DDR mutations were detected in 16.6% of urine and 15.4% of blood samples. BRCA1, BRCA2, CHEK2, ATM and NBN mutations were associated with significantly shorter PFS in response to conventional androgen deprivation therapy and first-line mCRPC therapy with abiraterone acetate. Additionally, BRCA1 and BRCA2 mutation-bearing patients had a significantly worse response to radium-223. However, DDR mutation status was predictive for the favourable effect of second-line abiraterone acetate after previous taxane-based chemotherapy. (4) Conclusions: Our data confirm the benefit of non-invasive urine-based genetic testing for timely identification of high-risk prostate cancer cases for treatment personalization.

Background: Ovarian cancer (OC) is the third most common and second most lethal onco-gynecological disease in the world, with high-grade serous ovarian cancer (HGSOC) making up the majority of OC cases worldwide. The current serological biomarkers used for OC diagnosis are lacking sensitivity and specificity, thus new biomarkers are greatly needed. Recently, the chromatin remodeling complex gene ARID1A, Notch and Wnt pathway gene expression, as well as HOX-related gene promoter methylation have been linked with promoting OC. Methods: In this pilot study, 10 gene expression biomarkers and 4 promoter methylation biomarkers were examined as potential diagnostic and prognostic indicators of OC in 65 fresh-frozen gynecologic tumor tissues. Results: Out of 10 genes analyzed, the expression of eight biomarkers was significantly reduced in OC cases compared to benign, and HOX-related gene promoter methylation significantly increased in OC tumors. Out of 14 biomarkers, CTNNB1 showed the best single biomarker separation of HGSOC from benign cases (AUC = 0.97), while a combination of the seven Notch pathway-related gene expressions (NOTCH1, NOTCH2, NOTCH3, NOTCH4, DLL1, JAG2, and HES1) demonstrated the best separation of HGSOC from the benign cases (AUC = 1). Conclusions: The combination of multiple gene expression or gene promoter methylation biomarkers shows great promise for the development of an effective biomarker-based diagnostic approach for OC.