The glycolytic PKM gene is associated with immune infiltrates and therapeutic response of pancreatic cancer

Background Cancer cells undergo metabolic reprogramming to sustain proliferation and metastasis, with the glycolytic pathway playing a key role. This study investigates the prognostic significance, immune infiltration, and treatment response of the glycolysis-related gene Pyruvate Kinase M (PKM) in pancreatic cancer. Methods Pancreatic cancer samples were obtained from GEO and TCGA databases. Glycolysis-related genes were identified using WGCNA and Msigdb, and PKM was selected via PPI network analysis and univariate Cox regression. Gene set enrichment analysis (GSEA), immune infiltration analysis (ESTIMATE), immune checkpoint inhibitor (ICI) response prediction (TIDE), and chemotherapeutic sensitivity analysis (pRRophetic) were conducted. Results PKM was identified as a key glycolysis-related gene. GSEA indicated that high PKM expression was associated with glycolytic processes and ERBB signaling. PKM was overexpressed in pancreatic cancer tissues, and patients with high PKM expression had significantly worse prognosis (P < 0.05). ESTIMATE analysis revealed a higher infiltration level of M0 macrophages in the high PKM expression group (P < 0.05). Additionally, high PKM expression correlated with reduced efficacy of ICI therapy (P < 0.05) and lower sensitivity to irinotecan and oxaliplatin (P < 0.05). Conclusion PKM plays a crucial role in glycolysis, immune regulation, and therapeutic response in pancreatic cancer. It may serve as a prognostic biomarker and a potential therapeutic target.