Identification of Key Genes Involved in Diabetic Peripheral Neuropathy Progression and Associated with Pancreatic...

Area of Science:

• Genomics
• Bioinformatics
• Oncology

Background:

• Diabetes mellitus (DM) is linked to increased morbidity, mortality, and cancer risk.
• Diabetic complications, such as peripheral neuropathy (DPN), and cancers like pancreatic cancer (PC) pose significant health challenges.

Purpose of the Study:

• Identify key genes in the pathogenesis of diabetic peripheral neuropathy (DPN).
• Identify key genes common to diabetes mellitus (DM) and pancreatic cancer (PC).
• Investigate the role of identified genes in patient survival and disease progression.

Main Methods:

• Analyzed gene expression profiles (GSE95849, GSE28735, GSE59953) to identify differentially expressed genes (DEGs).
• Utilized Gene Ontology (GO) and KEGG pathway analysis for functional enrichment.
• Constructed protein-protein interaction (PPI) networks using STRING and identified hub genes with Cytoscape (MCODE, cytoHubba).
• Performed survival analysis using Kaplan-Meier plotter and GEPIA.

Main Results:

• DPN-related DEGs were enriched in Toll-like receptor signaling, hematopoietic cell lineage, and chemokine signaling pathways, with TLR4, CCR2, and MMP9 identified as hub genes.
• DM and PC shared 58 DEGs enriched in ECM-receptor interaction, focal adhesion, and pathways in cancer. Five hub genes (PLAU, MET, CLU, APOL1, MMP9) correlated with PC patient survival.
• MMP9-correlated genes were linked to cancer tumorigenicity, insulin resistance, DM development, and inflammation.

Conclusions:

• Inflammation and immunity pathways are crucial in DM and DPN.
• ECM-receptor interaction, focal adhesion, and cancer pathways are significant in DM and PC.
• MMP9 shows potential as a prognostic marker for PC and a therapeutic target for DM, DPN, and PC.