Prognostic Significance of the Loss of Heterozygosity of KRAS in Early-Stage Lung Adenocarcinoma.
Prognostic Significance of the Loss of Heterozygosity of KRAS in Early-Stage Lung Adenocarcinoma.
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DOI：
10.3389/fonc.2022.873532
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发表时间：
2022
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
--
作者：
肺癌是一种常见病，预后差。涉及KRAS基因的基因组改变在肺癌中很常见，尽管关于不同的突变、缺失和表达如何影响疾病进程还不清楚。FDA最近首次批准了KRAS定向抑制剂。KRAS基因突变与肺腺癌预后不良有关，但KRAS杂合性缺失（洛）的意义尚未研究。在这项研究中，我们通过分析DNA拷贝数谱评估了早期肺腺癌中KRAS的洛缺失，并研究了mRNA表达和体细胞热点突变对患者预后的影响。KRAS突变存在于36%的病例中，并与mRNA表达升高相关。KRAS中的洛缺失与良好的预后相关，在KRAS突变患者中比在野生型患者中更显著。同时存在洛缺失和KRAS突变的患者预后优于KRAS突变。对于野生型肿瘤，在KRAS中有和没有洛缺失的患者之间没有观察到预后差异。我们的研究表明，KRAS的洛缺失是一个独立的预后因素，可以改善现有的肺腺癌的预后组。
Lung cancer is a common disease with a poor prognosis. Genomic alterations involving the KRAS gene are common in lung carcinomas, although much is unknown about how different mutations, deletions, and expressions influence the disease course. The first approval of a KRAS-directed inhibitor was recently approved by the FDA. Mutations in the KRAS gene have been associated with poor prognosis for lung adenocarcinomas, but implications of the loss of heterozygosity (LOH) of KRAS have not been investigated. In this study, we have assessed the LOH of KRAS in early-stage lung adenocarcinoma by analyzing DNA copy number profiles and have investigated the effect on patient outcome in association with mRNA expression and somatic hotspot mutations. KRAS mutation was present in 36% of cases and was associated with elevated mRNA expression. LOH in KRAS was associated with a favorable prognosis, more prominently in KRAS mutated than in wild-type patients. The presence of both LOH and mutation in KRAS conferred a better prognosis than KRAS mutation alone. For wild-type tumors, no difference in prognosis was observed between patients with and without LOH in KRAS. Our study indicates that LOH in KRAS is an independent prognostic factor that may refine the existing prognostic groups of lung adenocarcinomas.
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影响因子：
6.6
作者：
Bjaanæs MM;Fleischer T;Halvorsen AR;Daunay A;Busato F;Solberg S;Jørgensen L;Kure E;Edvardsen H;Børresen-Dale AL;Brustugun OT;Tost J;Kristensen V;Helland Å
通讯作者：
Helland Å
影响因子：
5.3
作者：
Brustugun, Odd Terje;Gronberg, Bjorn Henning;Solberg, Steinar Kristian
通讯作者：
Solberg, Steinar Kristian
影响因子：
3.7
作者：
Planck M;Edlund K;Botling J;Micke P;Isaksson S;Staaf J
通讯作者：
Staaf J
DOI：
10.1073/pnas.1904529116
发表时间：
2019-08-06
影响因子：
11.1
作者：
Kessler, Dirk;Gmachl, Michael;McConnell, Darryl B.
通讯作者：
McConnell, Darryl B.
影响因子：
45.3
作者：
Shepherd, Frances A.;Domerg, Caroline;Tsao, Ming-Sound
通讯作者：
Tsao, Ming-Sound