Identification of Blood-based Non-invasive Biomarkers and Therapeutic Agents against Pancreatic Ductal Adenocarcinoma (PDAC): A Network-based Study

Abstract

Pancreatic Ductal Adenocarcinoma (PDAC) is the most demolishing form of pancreatic cancer with poor prognosis and rising incidence. Difficulties in the early detection and aggressive biological nature of this disease are responsible for most of the therapeutic failures. In this study publicly available microarray expression data of full RNA from peripheral blood of PDAC patient has been utilized via network-based approach in order to identify potential non-invasive biomarkers and drug targets for early diagnosis and treatment of PDAC. Analysis of differentially expressed genes revealed their predominant involvement in translational process, apoptotic process, protein phosphorylation, immune responses, ATP binding, protein binding and signal transduction. Moreover, CREBBP, MAPK14, MAPK1, SMAD3, UBC, MAGOH, HSP90AB1, RPL23A, ACTB and STAT3 were identified as the best proteome signatures, GATA2, FOXC1, PPARG, E2F1, HINFP, USF2, MEF2A, FOXL1, YY1 and NFIC were identified as the best transcriptional regulatory signatures, and hsa-miR-93, hsa-miR-16, hsa-miR-195, hsa-miR-424, hsa-miR-506, hsa-miR-124, hsa-miR-590-3p, hsa-miR-1, hsa-miR-497 and hsa-miR-9 were identified as the best post-transcriptional regulatory signatures in PDAC patient. Analysis of drug-gene interaction revealed Anisomycin, Azactidine, Arsenic trioxide, Bortezomib, Ulixertinib and some other molecules as the probable candidate molecules which may reverse PDAC condition.