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 overa...

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Bibliographic Details
Main Authors: In Seok Yang, Sangwoo Kim
Format: Article
Language:English
Published: BMC 2018-02-01
Series:BMC Bioinformatics
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12859-018-2011-y
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Summary: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.
ISSN:1471-2105