Integrated Bioinformatics and Experimental Validation of Shared Genetic Targets in AKI and Ovarian Cancer for reserpine-based Therapeutics

¹ Centre for Emerging Diseases, Department of Biotechnology, Jaypee Institute of Information Technology, Sector-62, NOIDA, Uttar Pradesh, India 201309
² Department of Electronics and Communication Engineering, Jaypee Institute of Information Technology, Sector-62, NOIDA, Uttar Pradesh, India 201309

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Abstract

Introduction: Ovarian cancer (OC) is the most lethal and common malignancy among women. Patients with ovarian cancer are more susceptible to acute kidney injury (AKI) due to the side effect of chemotherapy, tumour burden and metastasis which can cause obstruction or direct invasion of the urinary tract, impairing renal function. Moreover, cytoreductive surgery combined with cisplatin-based chemotherapy also puts patients at risk of developing AKI. This study investigates the molecular links between OC and AKI, conditions that share overlapping pathogenic mechanisms but remain poorly understood in their interconnectedness. The study Identified the common differentially expressed genes (DEGs) and explore their potential as therapeutic targets, identify common pathways. Further the potential of phytocompound reserpine was evaluated as dual action on AKI and OC via molecular docking and in vitro experimentation.

The results identified twelve common genes between OC and acute AKI, with five genes (MDM2, EZH2, CD44, CCL5, IL1B) shown to be druggable targets through molecular docking with a reserpine. Pathway enrichment revealed shared involvement in signalling pathways regulating cell proliferation and repair. Reserpine exhibited selective cytotoxicity against ovarian cancer cells (SKOV3) without affecting kidney cells (HEK) in vitro and studied their anti-migratory properties on SKOV3 cells. These findings support a dual-target therapeutic approach that simultaneously mitigates tumour progression and renal injury in ovarian cancer patients, offering a promising strategy to improve both oncological outcomes and renal protection.