Vilas Deorao Nasare

A signature of circulating miRNAs predicts the prognosis and therapeutic outcome of taxane/platinum regimen in advanced ovarian carcinoma patients

Ovarian carcinoma (OC) is ranked as the eighth most lethal gynecological cancer due to late diagnosis and high recurrence. Existing biomarkers are lacking to predict the recurrence and stratify patients who are likely to benefit from chemotherapy. MicroRNAs (miRNAs/miRs) are persistently present in humans and are capable of predicting treatment outcomes. Thus, the purpose of the study was to assess the potential of circulatory miRNAs to predict the efficacy of OC. Newly diagnosed n = 208 OC patients were administrated neoadjuvant/adjuvant chemotherapy (taxane + platinum) after surgery. Their demographic, gynecologic, clinical parameters, response, and survival were recorded. MiR-27a, miR-182, miR-199a, miR-214, and miR-591 were taken and the expression were analyzed using real-time PCR at different treatment intervals. Further, its prognostic value (Kaplan-Meier, and Cox regression analysis) and diagnostic importance (receiver operating characteristic curve) were validated. The mean age of patients with poorly differentiated (45.2%) serous OC was 48.69 ± 10.38. The majority experienced menarche at ≥ 12 (62.2%) with poor menstrual hygiene (81.8%) and were post-menopausal (69.4%), some were associated with high risk of survival (HR =  > 1). MiRNA signature showed three over-expression and two under-expression (miR-27a, miR-182, and miR-214; miR-199a and miR-591) in advanced OC compared to the control (P=   1). ROC analysis showed enhanced the diagnostics accuracy (< 0.001). Our findings indicate that circulating miRNAs might be a potential minimally invasive diagnostic marker for treatment outcome and recurrence in ovarian carcinoma.

Clinicopathological insights and prognostic implications of DEK in association with apoptosis-regulating factors in ovarian cancer

Ovarian cancer is one of the most common gynecologic malignancies of the present era. Dysregulation of apoptosis is considered as one of the most important factors for malignant transformation. DEK is a ubiquitous protein, and its downregulation induces apoptosis by altering BCL-2, BAX, and CASPASE-3 expressions. This study illuminates the cumulative clinical usefulness of DEK and related apoptotic proteins. A total of 119 patients were enrolled during 2021-2023. Demographic and clinicopathological data were recorded at presentation, and the follow-up was done till August 2024. Tissue samples were analyzed using immunohistochemistry and real-time PCR. A paired t test assessed gene expression between normal and malignant tissues of different treatment strategies. The crosstab was performed to find the association of DEK, BCL-2, BAX, and CASPASE-3 with clinicopathological features. Pearson's correlation was used to predict the association of DEK with other apoptotic factors. Survival and hazard risk were evaluated using log-rank and Cox regression. The mean age of OC patients was 47.61 ± 12.5 years, presented with advanced stage (90.7%) and grade (85.3%). Most of them were post-menopausal (68.08%) and had unhygienic (76.5%) regular menstrual cycles (89.1%), and also experienced early pregnancy (61.8%). Some of these factors are related to a hazard risk (HR > 1). DEK and apoptotic proteins were upregulated in OC than in normal (p ≤ 0.01). DEK was positively correlated with BCL-2, BAX, and CASPASE-3, at both mRNA and protein levels, and only BAX showed significance in both (p ≤ 0.05). All the selected genes are independent risk factors for survival of OC (HR > 1), but only DEK and CASPASE-3 were significantly associated with poor survival (p ≤ 0.05). Dysregulation of DEK, CASPASE-3, and BAX/BCL-2 is associated with poor overall survival. Further, this study highlights the correlation between DEK and key apoptotic regulators, emphasizing the critical role of DEK in OC prognosis.

Assessment of quality of life among advanced ovarian cancer patients in a tertiary care hospital in India

The study aims to record the quality of life (Qol) and its changes while ovarian cancer (OC) patients undergo debulking surgeries and chemotherapy in a tertiary care hospital of Eastern India. Patients with advanced epithelial OC (FIGO stages III-IV) were recruited. They underwent primary/interval debulking surgeries with classical chemotherapy (adjuvant/neoadjuvant) of intravenous tri-weekly doses of paclitaxel + carboplatin. QoL was assessed using Fact- O + FACIT-Sp-12 questionnaire with a set of 51 questions in different domains (spiritual, physical, social, emotional, and functional factors) and a special set for OC patients under the heading "Additional concerns." The responses from patients were recorded at baseline (diagnosis/study entry), 2, 4, and 6 months during the treatment visits. Overall survival (OS) was assessed using Kaplan Meier curve. A majority of patients were 49.15±10.8 years of age, school-educated (54%), unemployed/homemakers (73.5%), belonging from rural setup (64.6%) with a monthly income of Rs. 2000/- to Rs. 5000/-. There was no statistically significant (p>0.05) improvement found in Qol from the baseline till the end of the study, neither overall nor in subsets (responders (Rs)/partial responders (PRs)/non-responder (NRs) groups or the adjuvant and neoadjuvant chemotherapy groups). The common toxicities like anemia, constipation, and weight loss were significantly (p<0.05) correlated with the patients' physical, functional, emotional, and social well-being. Ovarian cancer patients represent a poor functional, social, and disease-specific quality of life that needs to be addressed, identified, and improved by the growing nexus of healthcare providers and researchers.