Mutational status of main driver genes influences the prognosis of stage I-III lung adenocarcinoma patients underwent radical surgery

Background: The therapeutic strategies and prognosis of local advanced and metastatic lung cancer have been extensively investigated. However, the prognosis of early-stage lung cancer patients undergoing radical surgery has not been fully studied due to the difficulties in follow-up and assessment.

Methods: We recruited 447 stage I-III lung adenocarcinoma (LUAD) patients who underwent radical surgery and investigated the influence of main driver gene mutations and clinicopathological factors on patient overall survival (OS). Cancer tissue samples were collected retrospectively and mutational status and tumor mutational burden (TMB) were determined by whole-exome sequencing (WES).

Results: Distinct stage-dependent mutational frequency was revealed in main driver genes including EGFR, TP53, KRAS, STK11, ATM and NF1. Patients with TP53 mutations exhibited a trend of better survival than those with wild type TP53 (P=0.066), and STK11 mutations exhibited worse survival in stage III patients (P=0.031). EGFR mutations eliminated the across-stage difference in survival, which was still present in other wild type and mutant driver genes. Furthermore, patients with wild type TP53 appeared to have significantly worse survival than patients with other wild type driver genes in stage I (P<0.001). TMB cannot stratify the survival of LUAD patients in stage I-III. Age, gender, smoking status, smoking years, prior cancer history and cancer location had no stratification effect on patient survival, while T grading (P<0.001) and N grading (P<0.001) had significant stratification on survival.

Conclusions: TP53, EGFR and STK11 mutational status influenced the prognosis of stage I-III LUAD. T and N grading also stratified the patient survival. T grading was an independent risk factor.