Identification of the Genetic Association Between Type-2-Diabetes and Pancreatic Cancer

Biochem Genet. 2023 Jun;61(3):1143-1162. doi: 10.1007/s10528-022-10308-2. Epub 2022 Dec 9.

Abstract

Type-2-diabetes (T2D) and pancreatic cancer (PC) are both common diseases globally. Although T2D is reported as the adverse factor for predicting PC prognosis, its pathophysiology and relation with PC remain unknown. This study focused on exploring differentially expressed genes (DEGs) as well as their functional roles in T2D and PC, aiming to reveal the underlying association between the T2D and PC. To identify DEGs in T2D and PC, this study analyzed four microarray datasets obtained from Gene Expression Omnibus (GEO) database. Then, this work carried out enrichment as well as protein-protein interaction (PPI) network analysis for exploring DEGs-enriched functions and pathway. Besides, expression of hub genes was explored. TISIDB database was adopted to analyze the correlations among key gene and immune characteristics. Finally, the key gene expression was confirmed in vitro. DEGs were first screened from gene expression profiles of T2D and PC datasets, respectively. Then 135 common genes were identified in these four datasets. Based on functional analysis, common DEGs were mostly related to hormone secretion and metabolism pathways. Four hub genes were up-regulated, among which, MAFB was the most significant potential biomarker for PC. MAFB expression was strongly correlated with chemokines, chemokine receptors and immunomodulators. Finally, RT-qPCR was conducted to demonstrate the MAFB expression in T2D and PC. This study identified 15 hub genes with significant effects on the association of T2D with PC, and MAFB gene might be a biomarker for PC and had potential treatment value for PC.

Keywords: Bioinformatics; Biomarker; GEO; Pancreatic cancer; Type 2 diabetes.

MeSH terms

  • Biomarkers
  • Computational Biology
  • Diabetes Mellitus, Type 2* / genetics
  • Gene Expression Profiling
  • Humans
  • Pancreatic Neoplasms* / genetics

Substances

  • Biomarkers