Robust identification of shared key genomic biomarkers for diagnosis and therapies of pancreatic cancer with type-2 diabetes

Abstract

Abstract Background Pancreatic cancer (PC) and type-2 diabetes (T2D) are both complex diseases and they stimulate each other for which PC patients with T2D may reach to the severe condition quickly. So, the discovery of shared key genomic biomarkers (sKGBs), pathogenetic processes, and associated drug molecules is essential for simultaneous diagnosis and therapies. Methods Integrated robust statistics and bioinformatics tools and databases were employed to find the necessary results. Results We robustly identified 52 shared differentially expressed genes (sDEGs) that can separate both T2D and PC patients from the control samples. The protein-protein interaction (PPI) network analysis of sDEGs provided top-ranked six sDEGs (GAPDH, CASP1, MYD88, TNFRSF1A, TIMP1, TNFSF10) as the PC and T2D causing sKGBs. The random forest-based prediction and the Box-plot analyses results with TCGA and GTEx data significantly supported the association of sKGBs with both T2D and PC. Functional enrichment analysis of sKGBs significantly disclosed some crucial biological processes, molecular functions, and pathways that are associated with the development of both T2D and PC. The DNA methylation analyses results showed that five sKGBs (GAPDH, CASP1, MYD88, TNFRSF1A, TNFSF10) are hyper-methylated and enriched to the apoptosis processes which indicates the involvement of these sKGBs with the development and progression of PC. The immune infiltration level analyses indicated that the gene GAPDH is negative, and the rest five sKGBs are positively associated with different infiltrating immune cells. Finally, we suggested sKGBs-guided six candidate drug agents (NVP-BHG712, Olaparib, Irinotecan, Gliquidone, Herbacetin, and Linsitinib) by the screening through molecular docking, ADME/T, and DFT analysis for therapies of PC with T2D. Conclusions Individual studies on T2D and PC jointly supported our proposed sKGBs as both T2D and PC-causing genes. Similarly, sKGBs-guided drug molecules also received support as the candidate drug molecules for both T2D and PC. Therefore, the finding of this study might be valuable resources for diagnosis and therapies of PC with T2D.