Single-Cell Dissection of Prognostic Determinants in PDAC based on Single-Cell Transcriptomics and TCR Repertoire Analysis

Pancreatic ductal adenocarcinoma (PDAC) is characterized by an immunosuppressive tumor microenvironment and poor therapeutic responsiveness. While single-cell technologies enable high-resolution profiling, limited cohort sizes have constrained their application to prognostic inference. Paired single-cell RNA sequencing and T cell receptor sequencing were performed on 12 PDAC samples (4 primary tumors and 8 liver metastases). These data were integrated with large, prognostically annotated public bulk transcriptomic cohorts to construct continuous single-cell level risk scores, enabling systematic dissection of prognosis-associated heterogeneity across tumor and microenvironmental compartments. Prognostic heterogeneity in PDAC is not solely tumor-intrinsic but is profoundly shaped by immune and stromal ecosystems.