The prevalence and prognostic value of KRAS co-mutation subtypes in Chinese advanced non-small cell lung cancer patients.

Abstract

Objective KRAS mutation plays a critical role in the initiation and development of non‐small cell lung cancer (NSCLC). KRAS‐mutant patients exhibit diverse response to chemotherapy. KRAS co‐mutation subtypes and their prognosis value in advanced Chinese NSCLC patients remain largely elusive.MethodsA total of 1126 Chinese advanced NSCLC patients from Xiangya hospital were screened by capture‐based ultra‐deep sequencing for KRAS mutation between January 2015 and December 2016. Survival analyses were performed using Kaplan‐Meier analysis.ResultsAmong the patients screened, 84 cases were detected with KRAS mutation (7.5%). All of them were non‐squamous NSCLC and received pemetrexed plus platinum as the first‐line treatment. The most frequent KRAS co‐mutation genes were TP53 (29%), TP53/LKB1 (19%), and LKB1 (14%). Our data revealed that patients with KRAS co‐mutation had poorer prognosis in comparison with those harboring single KRAS mutation. Furthermore, patients with KPL (KRAS mutated with TP53 and LKB1) subtype, which was a novel subtype, had the shortest progression‐free survival (PFS) in all types of KRAS co‐mutation patients (P < .0001). The PFS and overall survival (OS) of patients with KRASG12D mutation were inferior than those with KRASG12C mutation or KRASG12Vmutation. Patients in KRASG>T type had significantly longer survival than those in KRASG>C type or KRASG>A type.ConclusionOur study revealed that concurrent genomic alterations can further stratify KRAS‐mutant lung adenocarcinoma patients into various subgroups with distinctive therapeutic responses and differential survival outcomes. The KPL is a novel and less responsive subtype among KRAS‐mutated NSCLC, and further investigation of effective treatment for this subtype is warranted.