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

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.

Identification of potential phytochemical for the inhibition of non-muscle invasive bladder cancer (NMIBC).

Non-muscle invasive bladder cancer (NMIBC) is one of the most common type of bladder cancer. Here, we have utilized an integrated transcriptomic-computational approach to identify alternate treatments to the NMIBC. In this study, we have performed the comprehensive comparative analysis between three groups of 36 patients with non-relapsed (NR), recurrence and progressive symptoms. Differentially expressed genes involved in the pathways associated with the NMIBC were identified. In silico protein-protein interaction (PPI) network was performed to create the network of the hub genes associated with NMIBC. Further, we compared NR individuals with two cohorts of patients with recurrent and progressive symptoms that lead to the identification of three major biomarkers CD34, FLT1 and WHSC1 genes. Concurrently, PPI also suggests that they are significant hub genes responsible for disease recurrence and progression. Furthermore, targeted genes WHSC-1 and FLT-1 were subjected to virtual screening for identification phytochemical inhibitors. Docking and molecular dynamics simulations concluded that the phytochemicals anonymously named 'UNK' and '6-hydroxycyanidin' are suitable for the inhibition of the proteins causing the 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 designing for the early treatment of the carcinomas.Communicated by Ramaswamy H. Sarma.