Drug repurposing analysis with co-expressed genes identifies novel drugs and small molecules for bladder cancer

Abstract

Bladder cancer (BC) is the fifth most common malignancy in humans and has poor survival rates. Although there is extensive research on the diagnosis and treatment of BC, novel molecular therapies are essential due to tumor recurrence. In this study, we aim to identify repurposed drugs or small molecules of BC with multi-omics systems biology perspective. Gene expression datasets were statistically analyzed by comparing bladder tumor and normal bladder tissues and differentially expressed genes (DEGs) were determined. Co-expression network of common DEGs for BC was constructed and co-expressed module was found by using tumors and control bladder tissues. Using independent data, we demonstrated the high prognostic capacity of the module genes. Moreover, repurposed drugs or small molecules were predicted by using L1000CDS2 gene expression based-search engine tool. We found numerous drug candidates as 480743.cdx, MK-2206, Geldanamycin, PIK-90, BRD-K50387473 (XMD8-92), BRD-K96144918 (mead acid), Vorinostat, PLX-4720, Entinostat, BIX-01294, PD-0325901 and Selumetinib, that may be used in BC therapy. We report 480743.cdx, BRD-K50387473 (XMD8-92) and mead acid as novel drugs or small molecules that offer crucial step in translational cancer research of BC.