Prognostic genes linking PD-1 resistance, hypoxia, and lactate metabolism in NSCLC: a multi-omics study

We initially identified a signature of 38 PD-1 inhibitor resistance-, hypoxia-, and lactate metabolism-associated genes from public NSCLC cohorts. Through rigorous bioinformatic analysis, seven core prognostic genes—CFTR, TLR2, GLS2, CAV1, TRIM28, MRPS16, and L1CAM—were pinpointed and used to construct a novel risk stratification model. To delineate the cellular context, scRNA-seq identified crucial cell types, including epithelial cells, ciliated cells, dendritic cells , and macrophages, and revealed dynamic changes in the expression of prognostic genes during differentiation. In the NSCLC group, RT-qPCR revealed significant downregulation of CAV1 and TLR2 and upregulation of MRPS16 and L1CAM. Our work bridges PD-1 inhibitor resistance, hypoxia, and lactate metabolism, offering fresh insights into NSCLC etiology and potential avenues for targeted intervention.