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

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.ope

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

Additional file 1: of Isoform specific gene expression analysis of KRAS in the prognosis of lung adenocarcinoma patients

Table S1. Somatic mutationand RNA-seq data files for LUAD. Table S2. Somatic mutation and RNA-seq data files for COAD, PAAD, and READ. Table S3. Median values of expression levels orproportions of K-Rasisoforms used for patient grouping. Table S4. Combined result of Cox regression analysis according to the states of K-Ras4A expression and proportionfor LUAD patients with KRAS mutations. (PDF 470 kb

Additional file 2: of Isoform specific gene expression analysis of KRAS in the prognosis of lung adenocarcinoma patients

Figure S1. Expression and proportion of K-Ras4A and K-Ras4B isoforms in COAD, PAAD, and READ. Figure S2. Linear regression analysis of KRAS mutations versus K-Ras4A expression, K-Ras4B expression, or K-Ras4A proportion in COAD, PAAD, and READ. Figure S3. Linear regression analysis of KRAS amplification versus K-Ras4A expression, K-Ras4B expression, or K-Ras4A proportion in COAD, PAAD, and READ cancer types. Figure S4. Overall survival of LUAD patients according to mutation states of KRAS mutations and pathological stages. Figure S5. Overall survival of LUAD patients according to the states of KRAS mutations and amplification. Figure S6. Disease-free survival of LUAD patients according to K-Ras4A expression and proportion. Figure S7. Integrative Genomics Viewer screen shots of aligned reads for three RNA-seq data sets of patients with KRAS mutations (SRX1741889, G12S (A); SRX174187, G13D (B); and SRX1741936, Q61H (C)). (PDF 638 kb