The Molecular Mechanisms of Cisplatin Resistance in Ovarian Cancer

Cisplatin is a cornerstone chemotherapeutic agent used to treat ovarian cancer. However, resistance to cisplatin represents a significant obstacle, often leading to treatment failure and poor prognosis. This study investigates the molecular mechanisms underlying cisplatin resistance in ovarian cancer using in silico approaches. The objective was to identify key genes, pathways, and molecular interactions associated with resistance and to propose potential therapeutic targets.MethodsWe employed a comprehensive bioinformatics pipeline integrating publicly available gene expression datasets from cisplatin-sensitive and resistant ovarian cancer samples. Differential gene expression analysis was performed to identify significant changes between the two groups. Gene ontology (GO) and pathway enrichment analyses were conducted to reveal biological processes and pathways implicated in resistance. Protein-protein interaction (PPI) networks were constructed to identify central hub genes. Furthermore, transcription factor (TF) and microRNA (miRNA) regulatory networks were predicted to explore upstream regulatory mechanisms. Drug-gene interaction databases were used to propose repurposable therapeutic agents targeting the identified mechanisms.ResultsOur analysis identified several differentially expressed genes (DEGs) enriched in pathways associated with DNA damage repair, apoptosis, and drug efflux. Key upregulated genes included ABCB۱, BRCA۱, and ERCC۱, while downregulated genes such as TP۵۳ and BAX were associated with apoptosis evasion. PPI analysis highlighted BRCA۱, EGFR, and AKT۱ as central hub genes. TF and miRNA network predictions implicated regulatory elements such as SP۱, TP۵۳, and miR-۲۱ in modulating cisplatin resistance. Drug repurposing analysis suggested potential agents like PARP inhibitors to target the identified resistance mechanisms.ConclusionThis in silico study elucidates the complex molecular mechanisms of cisplatin resistance in ovarian cancer, highlighting DNA damage repair, apoptosis, and drug efflux as critical processes. The identification of central hub genes and regulatory elements offers insights into potential therapeutic targets. These findings provide a foundation for future experimental validation and the development of strategies to overcome resistance.

کلیدواژه ها:

Cisplatin resistance ، ovarian cancer ، in silico analysis ، differential gene expression ، DNA damage repair