Abstract B011: Clinical correlation of PARP1, DNMT1 and GCS gene expression in ovarian cancer along with global methylation pattern (LINE1)
Authors: Luxmi Devi, Ashok Sharma, Lalit Kumar
Journal: Cancer Research (2025)

Abstract Background: Ovarian cancer remains one of the most important cancers causing gynaecological cancer-related mortality globally. Majority, 80% of patients are diagnosed at advanced stage (FIGO stage III-IV) of ovarian cancer. The standard treatment approach for advanced Epithelial Ovarian Cancer (EOC) is debulking surgery followed by adjuvant chemotherapy using taxane plus platinum. Resistance to platinum based chemotherapy remains a key reason for treatment failure in advanced (EOC).We aimed to investigate the relationship between the expression &amp; enzymatic activity of PARP1 and γ-GCS and correlate it with DNA methylation in ovarian cancer. Based on existing evidences, we hypothesized that PARP-1 or γ-GCS inhibition may lead to enhanced CDDP sensitivity in ovarian cancer. This study targets a better understanding of the molecular mechanism of platinum resistance and may help develop novel therapeutic strategies for ovarian cancer. Material and Methods: Peripheral Blood (PB) and Ascitic Fluid (AS) samples were collected from 20 EOC patients. The cohort was divided into two groups: Group A (n=10) included treatment-naive baseline patients, and Group B (n=10) comprised relapsed patients. Additionally, healthy control samples (n=10) were collected for comparison. The study involved:Gene Expression Analysis: Differential expression levels of PARP1, DNMT1, and γ-GCS were evaluated using qPCR.Enzymatic Activity Measurement: Glutathione (GSH) activity was quantified using ELISA.Global DNA Methylation Assessment: LINE1 methylation levels were measured via pyrosequencing to examine epigenetic changes. The resulting data were correlated with clinico-pathological parameters, including age, stage, CA markers, and hematological indices. Statistical analysis was conducted using GraphPad Prism 6, and a p-value &amp;lt; 0.05 was considered statistically significant. Results: High γ-GCS expression increases glutathione levels in newly diagnosed ovarian cancer patients, potentially driving platinum resistance. Consistent LINE1 hypermethylation across patients, influenced by various factors, highlights its potential as both a biomarker and a therapeutic target, paving the way for strategies to overcome chemotherapy resistance. Conclusion: In conclusion high GCS expression increases glutathione levels in PB of newly diagnosed ovarian cancer patients. Hypermethylation pattern of LINE1 was observed in all ovarian cancer patients. Methylation status of LINE1 is influenced by interaction between multiple factors. Keywords: Ovarian Cancer, cisplatin, PARP-1, γ –GCS and DNMT1, Glutathione, LINE1. Abbreviations: Epithelial Ovarian Cancer (EOC), cisplatin (CDDP), Glutathione (GSH), Gamma Glutamyl Cysteine Synthetase (γ-GCS), Poly (ADP ribosyl) polymerase-1 (PARP1), Enzyme-linked immunosorbent assay (ELISA), Quantitative Polymerase Chain Reaction (qPCR), DNA methylation LINE1, Peripheral Blood (PB), Ascitic Fluid (AS). Citation Format: Luxmi Devi, Ashok Sharma, Lalit Kumar. Clinical correlation of PARP1, DNMT1 and GCS gene expression in ovarian cancer along with global methylation pattern (LINE1) [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Methylation, Clonal Hematopoiesis, and Cancer; 2025 Feb 1-4; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2025;85(3 Suppl):Abstract nr B011.