Integrative Transcriptomic, Network, and Structure-Based Prioritization of Vitamin D۳-Associated Targets in Ovarian Cancer

Ovarian cancer is among the most fatal gynecologic malignancies, largely due to delayed detection, substantial molecular diversity, frequent relapse, and the limited durability of current therapeutic responses. Vitamin D۳ (VD۳) has been suggested to exert anticancer effects, but the molecular targets connecting VD۳ with ovarian cancer remain fragmented. This study aimed to identify potential VD۳-related therapeutic targets in ovarian cancer through integrated in silico validation. Ovarian cancer transcriptomic datasets, including GSE۱۴۴۰۷, GSE۱۸۵۲۰, and GSE۵۴۳۸۸, were obtained from the Gene Expression Omnibus. VD۳-related targets were predicted using SwissTargetPrediction and SEA. Overlapping disease–drug targets were analyzed using InteractiVenn, STRING ۱۲.۰, Cytoscape ۳.۱۰.۰, and cytoHubba. Functional enrichment was performed using DAVID and SRplot. Expression validation was performed using GEPIA۲ with TCGA-OV and GTEx data, while survival analysis was conducted using the TCGAbiolinks, survival, and survminer packages. Molecular docking was performed using MOE ۲۰۲۲.۰۲, and molecular dynamics simulation was conducted using YASARA Dynamics for ۵۰ ns. Network analysis identified nine hub genes: TNF, BCL۲, CCND۱, PGR, CCNA۲, KDR, AURKA, CHEK۱, and MAOB. GEPIA۲ validation showed significant dysregulation of eight hub genes, while survival analysis indicated that CHEK۱ and CCND۱ were significantly associated with overall survival. Docking showed favorable VD۳ docking scores ranging from −۵.۹۷ to −۱۰.۱۴ kcal/mol, with MAOB showing the strongest interaction. Molecular dynamics supported overall complex stability during a ۵۰-ns simulation. VD۳ may modulate ovarian cancer through interconnected targets involved in hormone response, cell-cycle control, oxidative metabolism, angiogenesis, and DNA damage regulation. Further in vitro and in vivo validation is required.

کلیدواژه ها:

In Silico ، network pharmacology ، ovarian cancer ، Vitamin D۳