Tumor Mutation Load: A Novel Independent Prognostic Factor in Stage IIIA-N2 Non-Small-Cell Lung Cancer

This study is aimed at investigating the prognostic biomarkers of patients with stage IIIA-N2 non-small-cell lung cancer (NSCLC) and at analyzing the correlation between tumor mutation load (the frequency and number of tumor mutations) and prognosis. Clinical data of 35 patients with stage IIIA-N2 NSCLC were collected from Cancer Hospital, Chinese Academy of Medical Sciences. Whole blood samples from the peripheral vein were taken at different treatment periods, and the mutations of cell-free DNA (cfDNA) were detected. Multivariate analysis showed that smoking (), mutation (), and max mutation () were associated with improved progression-free survival (PFS). The overall survival (OS) of well-differentiated NSCLC patients was better than that of poorly differentiated ones (). The rates of PFS, disease-free survival, local-regional recurrence-free survival, and local-regional progression-free survival were significantly higher in the group with a mutation than in the group with a mutation . The mutation number of the preoperation group was significantly higher than that of the postradiochemotherapy group (5 vs. 2.5, ), and the max mutation frequency change was approximately significant in the postradiochemotherapy group compared with the postoperation group (2.6% vs. 1.85%, ). The max mutation frequency is positively correlated with vascular invasion (21.13% vs. 3.62%, ). Furthermore, Met, ALK, APC, PTEN, ERBB4, NF1, and other genes, involving multiple tumor suppressor genes and lung cancer-driven genes, did not mutate in recurrence-free patients when compared with recurrent patients. In conclusion, differentiation, smoking, mutation , and mutation are prognostic factors. The frequency and number of gene mutations in cfDNA are expected to be prognostic predictors of NSCLC.