Novel integrated Omics based computational approach for drug repurposing for non-muscle invasive bladder cancer (NMIBC)

Abstract

Non-muscle invasive bladder cancer (NMIBC) refers to a subtype of bladder carcinoma where cancer is localized in the inner lining of bladder. NMIBC consider as one of most costly malignancy and requires significant surgical and therapeutic measure. However, recurrence and progression of tumor is common in treated patients. Here we presented an integrated OMICs approach for the identification and inhibition of NMIBC specific genes. We utilized a case study where three group of patients were compared: 1) Relapsed tumors 2) recurrent tumors and 3) tumor in progression. Common transcriptome signature between patients facing recurrence and progression allowed us to identify three NMIBC specific genes FLT-1, WHSC-1 and CD34. We further utilized novel approach of Co-expressed gene-set enrichment analysis (COGENA) on the differentially expressed genes of this case study. Three drugs (paroxetine, adiphenine and H-89) with role of receptors inhibition were identified and predicted as repurposed drugs for the inhibition NMIBC specific genes. We further tested this hypothesis by performing molecular docking and simulation analysis between cancer specific proteins and drugs. FLT-1 have shown significant stable interaction with both drugs paroxetine and adiphenine whereas WHSC-1 have shown compact interaction with adiphenine and H-89. In the light of these evidence, we suggest that adiphenine could be repositioned as alternate targeted medicine for the treatment of NMIBC. In the future, this study will help for strengthening the strategies development at the molecular level for the control of carcinomas at early as well as detection of active and binding site, receptor-ligand interaction and also make drug repurposing for the early treatment of the carcinomas.

Communicated by Ramaswamy H. Sarma

Keywords:

• Drug repurposing
• bladder cancer
• urothelial carcinoma
• paroxetine
• adiphenine
• COGENA

Author contribution

Conceptualization, T.L., L.S., W.U.H; methodology, T.L., W.U.H., L.S., Z.W., Y.S., M.U.K; software, Z.W., Y.S.,W.H., Q.T, Q.S.; validation, Y.S.,T.L., L.S., S.S.; formal analysis, W.L., T.L., Q.T., W.H., S.S.,; writing, original draft preparation, W.U.H., T.L., L.S., S.S; writing, review and editing S.S., T.L., L.S., Q.T., Z.W., Y.S., supervision, L.S., SS .All authors have read and agreed to the published version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

No funding was utilized for the completion of this project.