Prediction of biomarker signatures and therapeutic agents from blood sample against Pancreatic Ductal Adenocarcinoma (PDAC): A network-based study

Abstract

Pancreatic Ductal Adenocarcinoma (PDAC) is a 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 the peripheral blood of PDAC patients has been utilized via a 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 the translational process, apoptotic process, protein phosphorylation, immune response, 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 patients. Analysis of drug-gene interactions revealed Anisomycin, Azactidine, Arsenic trioxide, Bortezomib, Ulixertinib, and some other molecules as probable candidate molecules which may reverse the PDAC condition.