A T-cell exhaustion-associated immune microenvironment signature for lung adenocarcinoma prognosis

Lung adenocarcinoma (LUAD) is characterised by high heterogeneity and a complex tumour microenvironment (TME). Identifying reliable prognostic markers associated with the immune microenvironment is crucial for improving personalised treatment for patients with LUAD. In this study, we constructed a prognostic risk model for LUAD patients using T-cell exhaustion-associated genes identified from exploratory single-cell RNA-seq analysis, and systematically evaluated its ability to predict survival and immune infiltration using bulk transcriptomic data and machine learning algorithms. Subsequently, we used real-time quantitative PCR (qRT-PCR) to detect differences in the expression of the core genes in the model (PTTG1 and BIRC3) in human normal bronchial epithelial cells (BEAS-2B) and LUAD cell lines (A549, H1299). Finally, we further validated the role of PTTG1 in LUAD cell proliferation by knocking down PTTG1 using siRNA in combination with CCK-8 assays. We successfully constructed a prognostic model comprising genes associated with the immune microenvironment, which demonstrated excellent performance in predicting survival. In vitro results showed that the expression levels of the core high-risk genes PTTG1 and BIRC3 were significantly higher in LUAD cells than in normal control cells. Knockdown of PTTG1 significantly inhibited the in vitro proliferation capacity of A549 and H1299 cells. The prognostic model established in this study serves as an effective tool for predicting survival in LUAD patients. In vitro experiments confirmed the role of core model genes in promoting tumour proliferation, providing potential candidate targets for targeted therapy in LUAD.