Alternative splicing expands the prognostic impact of KRAS in microsatellite stable primary colorectal cancer.

ABSTRACT: KRAS mutation is a well-known marker for poor response to targeted treatment and patient prognosis in microsatellite stable (MSS) colorectal cancer (CRC). However, variation in clinical outcomes among patients wild-type for KRAS underlines that this is not a homogeneous population. Here, we evaluated the prognostic impact of KRAS alternative splicing in relation to mutation status in a single-hospital series of primary MSS CRCs (N = 258). Using splicing-sensitive microarrays and RNA sequencing, the relative expression of KRAS-4A versus KRAS-4B transcript variants was confirmed to be down-regulated in CRC compared to normal colonic mucosa (N = 41; p ≤ 0.001). This was independent of mutation status, however, gene set enrichment analysis revealed that the effect of splicing on KRAS signaling

SUBMITTER: Eilertsen IA 

PROVIDER: S-EPMC6587976 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature