Integrative Single-Cell and Bulk RNA Sequencing Identifies a Glycolysis-Related Prognostic Signature for Predicting Prognosis in Pancreatic Cancer

Alterations in glycolysis play a crucial role in cancer cells, influencing tumor aggressiveness and therapeutic effect, particularly in pancreatic adenocarcinoma (PAAD). However, the specific glycolysis-related genes involved in PAAD progression remain poorly understood. This study established glycolysis-related molecular subtypes with distinct survival outcomes using TCGA datasets. The favorable prognosis subtype exhibited enhanced immune infiltration and an activated tumor microenvironment. A glycolysis prognostic model effectively predicted PAAD survival, correlating with global glycolytic pathways, and AUCell evaluated neutrophil communication networks of models. Functional validation demonstrated that ENO1/PGM2L1 co-expression promoted tumor proliferation, migration, invasion, and glycolytic flux in vitro, while accelerating xenograft growth in vivo. Conversely, their knockdown suppressed malignancy. Our study demonstrated that the glycolytic prognostic risk model serves as a reliable tool for prognosis and prediction of PAAD progression. ENO1 and PGM2L1 emerge as key risk factors promoting the malignant progression of PAAD.