Clinical Characteristics And Prognosis Significance Of Driver Oncogenes In Chinese Lung Adenocarcinoma

Objectives Driver oncogenes’ expression in lung adenocarcinoma varies greatly among different populations, and lacks of large sample study on Chinese population for multiple driver oncogenes. The prognosis role of driver oncogenes in lung adenocarcinoma is also controversial. The purpose of this study was to detect the presence of driver oncogenes, such as EGFR、KRAS、ALK、RET、BRAF, and to evaluate their associations with clinicopathological features and prognosis in Chinese lung adenocarcinoma.Methods The expression of driver oncogenes, such as EGFR、KRAS、ALK、RET、BRAF, were detected by fluorescence quantitative PCR in tumor tissues of 432 lung adenocarcinoma patients with complete follow-up data. The correlation of gene expression and clinicopathological features is retrospectively analyzed. Kaplan-Meier survival curves are used to evaluate the correlation of these genes and patients’ prognosis, COX univariate and multivariate regression analysis is used to assess the correlation of gene expression and disease-free survival and survival time.Results Among tissue samples of 432 patients with lung adenocarcinoma, the positive rate of EGFR, KRAS, ALK, RET, BRAF was 48.8%, 12.0%, 3.2%, 1.2%, 0.5% respectively. Our study found no cases of double gene or multiple gene mutation. The overall lung adenocarcinoma driver gene detection rate was 65.7%. Our study shows that EGFR mutations were more common in women, non-smokers or light smokers, lepidic predominant invasive adenocarcinoma subtype and in patients with moderately or well-differentiated; KRAS mutations were more common in heavy smokers, mucinous invasive adenocarcinoma subtype, well-differentiated, early stage patients. ALK positives were more common in younger than 55 years old, solid predominant invasive adenocarcinoma subtypes, moderately-poorly differentiated or poorly differentiated, late stage especially N2 stage patients. Survival analysis showed that male, younger than 55 years old, mass>3cm, late T/N/M stage, surgical residual positive, poorly differentiation, tumor thrombus patients were apt to recurrence(P<0.05); Male, heavy smoking, mass>3cm, late T/N/M stage, surgical residual positive, solid predominant invasive adenocarcinoma subtypes, poorly differentiation, pleural invasion, tumor thrombus, wall infiltration were associated with increased risk of early death after surgery(P<0.05). The prognosis survival analysis for driver gene showed that EGFR, ALK gene-positive in each stage subgroups are nothing to do with the recurrence and survival; KRAS gene mutations in patients with early stage has nothing to do with the recurrence and survival, while KRAS mutations in stage IIIA patients indicate shorter DFS and OS(P=0.022 、 0.043); EGFR/KRAS/ALK-driven gene positive group and triple-negative group have no significant difference in the DFS and OS. COX multivariate analysis showed that male, late stage are associated with increased risk of early recurrence; heavy smoking, late stage, late N stage, mass>3cm, poorly differentiation are associated with increased risk of early death after surgery; the mutation status of driver gene are not independent factors for DFS or OS.Conclusions Q-PCR can detect 65.7% driver genes in lung adenocarcinoma. Each group with different gene has different clinical and pathological features. KRAS mutations indicate poor prognosis only in patients with stage IIIA, while EGFR, ALK gene are not prognostic factors in lung adenocarcinoma.