Association of the KRAS genotype and clinicopathologic findings of resected non-small-cell lung cancer: A pooled analysis of 179 patients
Association of the KRAS genotype and clinicopathologic findings of resected non-small-cell lung cancer: A pooled analysis of 179 patients
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DOI：
10.1016/j.cancergen.2022.09.004
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发表时间：
2022-09-28
期刊：
影响因子：
1.9
通讯作者：
Matsushita, Hirokazu
中科院分区：
文献类型：
--
作者：
Masago, Katsuhiro;Kuroda, Hiroaki;Matsushita, Hirokazu
背景资料：本研究评估了早期KRAS突变非小细胞肺癌的临床病理学背景，并使用RNA测序程序分析了KRAS突变肿瘤的生物学过程。我们使用了一组连续的179例手术切除的携带KRAS突变的早期非小细胞肺癌，并分析了临床病理特征，包括KRAS基因型，影响无复发生存率和预后。因此，我们进行了RNA测序，以确定十九KRAS突变的非小细胞cancer.Results的基因表达谱：最常见的KRAS基因型是p.G12C（57; 31.8%）。高p分期（风险比[HR]，4.181; P < 0.0001）和以实体为主的腺癌组织学（HR，2.343; P = 0.0076）是无复发生存率的重要独立预后因素。高p分期（HR，3.793; P <0.0001）、以实体为主的腺癌组织学（HR，2.373; P = 0.0147）和KRAS p.G12V基因型（HR，1.975; P = 0.0407）是总生存期的显著独立预后因素。对这两个因子的基因表达分析显示，p.G12V基因型更接近干细胞的基因型，并且具有增强脂肪酸和氨基酸代谢的特性。同时，一个坚实的优势表型被证明是获得的一个性状，可以承受缺氧和木兰素-内过氧化物合酶的影响。KRAS p.G12V基因型和实性为主腺癌表型可能是切除的早期非小细胞肺癌临床病程较差的独立预测因素，这可能是由于在干细胞中观察到的分化趋势，增强脂肪酸和氨基酸代谢的特性，以及野牡丹素-内过氧化物合酶的作用。(C)爱思唯尔公司All rights reserved.
Background: This study assessed the clinicopathological background of early-stage KRAS-mutated nonsmall-cell lung cancer and analyzed the biological process of KRAS-mutated tumor using an RNA sequencing procedure.Patients and methods: We used a cohort of consecutive series of 179 surgically resected early-stage nonsmall-cell lung cancers harboring KRAS mutations and analyzed the clinicopathological features, including the KRAS genotypes, affecting the recurrence-free survival and prognosis. Consequently, we performed RNA sequencing to determine the gene expression profiles of nineteen KRAS-mutated non-small-cell cancers.Results: The most common KRAS genotype was p.G12C (57; 31.8%). A high p-stage (hazard ratio [HR], 4.181; P < 0.0001) and solid predominant adenocarcinoma histology (HR, 2.343; P = 0.0076) were significant independent prognostic factors for the recurrence-free survival. A high p-stage (HR, 3.793; P < 0.00 01), solid predominant adenocarcinoma histology (HR, 2.373; P = 0.0147), and KRAS p.G12V genotype (HR, 1.975; P = 0.0407) were significant independent prognostic factors for the overall survival. A gene expression analysis of the two factors revealed the p.G12V genotype to be closer to those of stem cells, and the traits of e an enhanced fatty acid and amino acid metabolism. as well as And a solid predominant phenotype were shown to an acquired a trait that can withstand hypoxia and the effect of prostaglandin-endoperoxide synthase.Conclusion: : The KRAS p.G12V genotype and solid predominant adenocarcinoma phenotype may be independent predictive factors of a poor clinical course in resected early-stage non-small-cell lung cancers, possibly due to the differentiation tendency observed in stem cells, the trait of an enhanced fatty acid and amino acid metabolism, and the effect of prostaglandin-endoperoxide synthase. (C) 2022 Elsevier Inc. All rights reserved.