Integrated analysis of single-cell and bulk RNA sequencing to construct a CD8 + T cell-related immune gene signature in pancreatic cancer

Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor that responds poorly to immunotherapy. The pivotal influence of CD8 + T-cell infiltration on immunotherapy has been documented in various solid tumors. However, the specific contribution of CD8 + T cell-associated immune genes (TIGs) to the tumor immune microenvironment remains unclear. Methods: We obtained CD8 + T cell-related immune genes from the INNATE and IMMPORT databases. Univariate analysis and lasso regression analysis were utilized to screen hub TIGs and develop a prognostic signature, the TIGs score. This score was used to evaluate prognosis, immunocyte infiltration, cancer-associated signaling pathways, and the potential responsiveness of immunotherapy. The transcriptomic data and single-cell data from the GSE183795 and GE212966 datasets are employed to validate the reliability of the findings. Results: Our findings suggest that patients with low TIGs scores have stronger immune effector functions and immune checkpoint activation, resulting in a more favorable response to PD-L1 inhibitors. TIGs scores were significantly correlated with various molecular characteristics and clinical outcomes, such as tumor mutation burden, multiple tumor-associated pathways, and chemotherapeutic drug sensitivity. PSME2 was identified as a potential prognostic biomarker for predicting survival in patients with PDAC. Conclusions: This study elucidates the intricate regulatory mechanisms of TIGs within the tumor immune microenvironment of pancreatic cancer. Our findings strongly suggest that the TIGs score is a robust prognostic marker for prognosis and immunotherapy responsiveness. Additionally, targeting PSME2 may offer a novel avenue for enhancing the effectiveness of immunotherapy in pancreatic cancer.