【Abstract】 Objective Lung adenocarcinoma (LUAD) has a poor prognosis. This study aimed to screen for core prognostic genes associated with the tumour microenvironment (TME) and programmed cell death (PCD) to provide new prognostic markers and therapeutic targets for LUAD and to validate their cross-species conservation. Methods Based on RNA-seq data from LUAD and normal lung tissue in the TCGA database, the ESTIMATE algorithm was used to assess the TME and screen for differentially expressed genes (DEGs). Functional enrichment (GO/KEGG) and protein-protein interaction (PPI) network analyses were performed on the DEGs. Core prognostic genes were identified through a combination of univariate COX regression and PCD genomic cross-screening. Their prognostic value and TME association were validated through survival analysis, genomic enrichment (GSEA), and immune infiltration (CIBERSORT) analysis. Results High immune/ESTIMATE scores were significantly associated with prolonged patient survival. The selected shared DEGs were primarily enriched in immune-related pathways. Cross-analysis identified CD19 and CD79A as core prognostic genes. Clinical feature analysis showed that CD19 and CD79A expression was significantly higher in LUAD tumour tissues than in normal lung tissues, but their expression levels decreased significantly with advancing TNM staging, closely associated with advanced staging, distant metastasis, and poor prognosis. Survival analysis indicated that LUAD patients with high CD19/CD79A expression had significantly longer overall survival than those with low expression. Animal experiment validation confirmed the cross-species conserved role of CD19/CD79A in tumour progression. GSEA analysis indicated that the high-expression group of CD19/CD79A was significantly enriched in immune activation pathways (such as allograft rejection and complement response), while the low-expression group was enriched in metabolic (glycolysis, oxidative phosphorylation) and oncogenic pathways. Immune infiltration (CIBERSORT) analysis further confirmed that their expression levels were significantly positively correlated with TME immune activity. Conclusion CD19 and CD79A are overexpressed in LUAD tumour tissues, but their expression levels decrease with disease progression. High expression of CD19/CD79A is closely associated with favourable prognosis and immune-activated TME, while low expression suggests poor prognosis and is associated with immune suppression/oncogenic states. They may serve as potential protective prognostic biomarkers and immunotherapy targets for LUAD, providing insights into LUAD immune mechanisms and guiding the development of B-cell-targeted therapeutic strategies.