Lung cancer pathogenesis and poor response to therapy were dependent on driver oncogenic mutations.

AIMS: Lung cancer was the most fatal malignancy, dominated the cancer related mortality list for years, and we tried to distinguish the lung adenocarcinoma patients at higher risk from those bearing lower therapy resistance and recurrence risk.

MATERIALS: Patients information from clinical Sequencing Cohorts and from the Regional Medical Center of the Middle-West China were included. The whole-exome sequencing was analyzed for risk evaluation.

KEY FINDINGS: We found that Smoking stimulated the oncogenic genes mutations, and the most frequently mutated genes of EGFR, KRAS, and TP53 (E/K/P) were identified. Different N stage affected the survival prognosis of patients bearing E/K/P mutations, but the T stage and AJCC stage did not. Radiation failed to prolong survival of phase II/III patients who didn't receive surgery. In those received surgery, radiation also failed to prolong survival of phase II/III patients. Radiation did not improve the prognosis in patients bearing E/K/P mutation burdens, whose differences were identified in gender or smoking-history classified groups.

SIGNIFICANCE: Smoking status and history contributed to oncogenic mutation burdens associated therapy resistance, and the aggressive treatment, especially to radiation, may lead to worse therapy response to current and past smoking behavior.