Background: Longstanding type 2 diabetes mellitus (T2DM) is an increased risk of pancreatic cancer (PC) in western populations, and PC is also a cause of T2DM. However, the association of glucose metabolism between T2DM and PC remains unclear.
Methods: Differentially expressed genes (DEGs) were identified by bioinformatic analysis from Gene Expression Omnibus (GEO) datasets GSE20966 and GSE16515, respectively. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, Gene Set Enrichment Analysis (GSEA), the Kaplan-Meier (KM) Plotter and Tumor Immune Estimation Resource (TIMER) database were applied. Pancreatic cancer cell lines and primary PDAC samples were used. Cell culture, immunohistochemistry (IHC), siRNA transfection, Western blot, RT-PCR, and migration assay, animal xenograft model studies and statistical analysis were performed in this study.
Results: We identified 64 DEGs in GSE20966 of T2DM, and 296 DEGs were identified in GSE16515 of pancreatic cancer, respectively. T2DM-DEGs were mainly enriched in synaptic vesicle cycle, protein export. KEGG pathways in pancreatic cancer included spliceosome, RNA transport. Here, ISG20L2 was identified as only a co-expressed gene between T2DM and PDAC. We found that the expression of ISG20L2 was associated with tumor immune cell infiltration. ISG20L2 was significantly upregulated in PDAC and associated with prognosis of PDAC patients. Moreover, ISG20L2 expression was regulated by GLUT1 , HK2 , LDHA , PKM1 and PKM2 related with glycolysis in PDAC. ISG20L2 promoted PDAC cell proliferation and migration both in vitro and in vivo.
Conclusion: This study showed that ISG20L2 promoted the progression and ISG20L2 may be a potential therapeutic strategy in PDAC.