Table 3_Transcription factor-driven metabolic stratification reveals glycolytic and lipogenic subtypes with distinct prognostic and functional features in pancreatic cancer.docx

However, the contribution of transcription factor (TF)-driven regulatory programs to metabolic subtype stratification remains poorly understood. This study aims to determine whether TF-based classification can identify prognostically relevant glycolytic and lipogenic PDAC subtypes.</p>Methods<p>Bulk transcriptomic data from multiple PDAC cohorts and single-cell RNA sequencing data were integrated to characterize TF-associated metabolic heterogeneity.

Metabolic signatures and TFs were quantified using single-sample gene set enrichment analysis (ssGSEA) and AddModule Score (AMS). Differential expression, enrichment analysis, integrative bulk and single-cell transcriptomic analysis, and deep neural network-based metabolic flux modeling were performed to investigate metabolic programs and functional differences between TF-defined subtypes. Additionally, RNA interference, RT-qPCR, lipid droplets staining, lactate assay, and transwell assays were used to evaluate the roles of TP63 in metabolic regulation.</p>Results<p>Glycolytic and lipogenic TF-defined metabolic subtypes were identified across multiple independent PDAC cohorts.