miRNA-mediated metabolic reprogramming is associated with recurrence in ovarian cancer.

Abstract

Background: Ovarian cancer (OC) recurrence and therapy resistance remain major clinical challenges. Identifying the molecular adaptations associated with relapse is essential for improving disease monitoring.

Research design and methods: We performed miRNA expression profiling on tissue and serum samples obtained from different primary ovarian cancer (POC) (n = 8) and recurrent ovarian cancer (ROC) cases (n = 8). Following statistical filtering, target prediction and functional pathway enrichment analyses were conducted. Clinical prognostic associations of target genes were explored using the Kaplan-Meier Plotter database.

Results: A candidate recurrence-associated signature was identified, comprising hsa-miR-3656 (tissue, Fold Change >1.8), hsa-miR-4701-5p, and hsa-miR-6775-3p (serum, Fold Change >2.0), all significantly upregulated in ROC. Computational target analysis identified 375 miRNA-mRNA interactions primarily enriched in sphingolipid and purine metabolism pathways. Evaluation of the target genes indicated that altered expression of DEGS1, NPR1, and ALDH1B1 is correlated with poorer progression-free survival.

Conclusions: OC recurrence is associated with a distinct miRNA profile linked to metabolic reprogramming. Although functional validation is required, circulating hsa-miR-4701-5p and hsa-miR-6775-3p represent candidate liquid biopsy biomarkers requiring prospective validation for recurrence monitoring.