Integrative analysis reveals distinct subtypes with therapeutic implications in KRAS-mutant lung adenocarcinoma.

ABSTRACT:

Background

KRAS-mutant lung adenocarcinomas (LUADs) are heterogeneous and frequently occur in smokers. The heterogeneity of KRAS-mutant LUAD has been an obstacle for the drug discovery.

Methods

We integrated multiplatform datatypes and identified two corresponding subtypes in the patients and cell lines. We further characterized the features of these two subtypes and performed drug screening to identify subtype-specific drugs. Finally, we used the defining features of the KRAS subtypes for drug sensitivity prediction.

Findings

Patient-Subtype 1 (PS1) was characterized by increased smoking-related mutational signature activity, a low tumor-infiltrating lymphocyte (TIL)-associating score and STK11/KEAP1 co-mutations. Patient-Subtype 2 (PS2) was characterized by an incre

SUBMITTER: Liu K 

PROVIDER: S-EPMC6197714 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature