Isoform specific gene expression analysis of KRAS in the prognosis of lung adenocarcinoma patients.

ABSTRACT: BACKGROUND:Aberrant mutations in KRAS play a critical role in tumor initiation and progression, and are a negative prognosis factor in lung adenocarcinoma (LUAD). RESULTS:Using genomic analysis for K-Ras isoforms (K-Ras4A and K-Ras4B) and large-scale multi-omics data, we inspected the overall survival (OS) and disease-free survival (DFS) of LUAD patients based on the abundance of transcript variants by analyzing RNA expression and somatic mutation data from The Cancer Genome Atlas (n =?516). The expression of the minor transcript K-Ras4A and its proportion were positively correlated with the presence of KRAS mutations in LUAD. We found that both K-Ras4A abundance measures (expression and proportion) have a strong association with poor OS (p =?0.0149 and p =?3.18E-3, respectively) and DFS (p =?3.03E-4 and p =?0.0237, respectively), but only in patients harboring KRAS mutations. A Cox regression analysis showed significant results in groups with low expression (hazard ratio (HR)?=?2.533, 95% confidence interval (CI)?=?1.380-4.651, p =?2.72E-3) and low proportion (HR?=?2.549, 95% CI?=?1.387-4.684, p =?2.58E-3) of K-Ras4A. CONCLUSIONS:Based on the above results, we report the possible use of abundance measures for K-Ras4A for predicting the survival of LUAD patients with KRAS mutations.

SUBMITTER: Yang IS 

PROVIDER: S-EPMC6389035 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature