Development and external validation of a composite immune-clinical prognostic model associated with EGFR mutation in East-Asian patients with lung adenocarcinoma

BACKGROUND: EGFR mutation is a common oncogene driver in East Asians with lung adenocarcinoma (LUAD), conferring a favorable prognosis with effective targeted therapy. However, the EGFR mutation is a weak predictor of long-term survival. Therefore, a powerful predictive tool is urgently needed to estimate disease prognosis and patient survival for East-Asian patients with LUAD. METHODS: In this first systematic analysis of the relationships among EGFR mutation, immunophenotype, and prognosis in LUAD samples from East-Asian patients, we constructed a prognostic signature consisting of EGFR-associated immune-related gene pairs (EIGPs). The predictive performance for overall survival (OS) and the clinical significance of this signature were then comprehensively investigated. RESULTS: Based on transcriptome data analysis of a training set, we proposed the EIGP index (EIGPI), represented by five EIGPs, which was significantly associated with the OS of East-Asian patients with LUAD. It was also well validated in a test set. Furthermore, the prognostic performance of the EIGPI was further verified using protein levels in an additional independent set. Stratification analysis and multivariate Cox regression analysis revealed that the EIGPI was an independent prognostic factor. When combined with stage, the composite immune-clinical prognostic model index (ICPMI) showed improved prognostic accuracy in all datasets. CONCLUSION: This study was the first to systematically investigate the relationships among EGFR mutation, immunophenotype, and prognosis in East Asians with LUAD and develop a composite clinical and immune model associated with EGFR mutation. This model may be a reliable and promising prognostic tool and help further personalize patient management.