scRNA-Seq Combined with scPagwas Analysis Identifies GNG7 as a Core Gene in Lung Adenocarcinoma

Objective: Lung cancer is a leading cause of cancer-related deaths globally, with lung adenocarcinoma (LUAD) showing high incidence in non-smoking cases. Over one million die annually from lung cancer, and LUAD presents treatment challenges due to complex biological behavior, variability in therapeutic responses, and pronounced heterogeneity (within tumor cells and the microenvironment). This study integrates single-cell RNA sequencing (scRNA-Seq) and genome-wide association study (GWAS) data to identify LUAD-associated cell subpopulations and core genes, offering insights into pathogenesis and potential therapeutic targets/prognostic biomarkers. Methods: The GSE196303 single-cell transcriptomic dataset (3 adjacent normal, 3 tumor tissues) was analyzed via Seurat and Harmony for clustering, annotation, and batch correction. Combined with GWAS summary data (1002 cases, 462008 controls), scPagwas identified trait-associated subpopulations. Using TCGA-LUAD bulk RNA-seq (541 tumors, 59 adjacent tissues) and clinical data, BayesPrism quantified cell subtype abundance. Limma, WGCNA, somatic mutation analysis, and immune infiltration assessment (ssGSEA, CIBERSORT) explored clinical associations. Drug sensitivity was predicted via oncoPredict, with survival analysis and Cox regression screening prognostic markers. Results: Eleven cell subpopulations were identified; CD8+ T cells had significantly higher trait-related scores (TRS, P<0.05). BayesPrism showed CD8+ T cell abundance was upregulated in LUAD and linked to favorable prognosis (P<0.05). Effector CD8+ T cell abundance correlated with gender, TNM stage, and survival, with high-abundance patients more sensitive to drugs like Savolitinib (P<0.05). TP53 and STK11 mutations associated with effector CD8+ T cell abundance. WGCNA and differential expression screening identified GNG7 as a core gene linked to effector CD8+ T cells, with high expression significantly improving survival (P=0.004). Conclusion: CD8+ T cells are a core LUAD subpopulation, with abundance correlating with clinical characteristics and the immune microenvironment. GNG7 is a core gene associated with effector CD8+ T cells.