Prognostic features and comprehensive genomic analysis of NF1 mutations in EGFR mutant lung cancer patients.
Prognostic features and comprehensive genomic analysis of NF1 mutations in EGFR mutant lung cancer patients.
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DOI：
10.1002/cam4.4925
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发表时间：
2023-01
期刊：
影响因子：
4
通讯作者：
Wu, Yi-long
中科院分区：
文献类型：
--
作者：
Tian, Hong-xia;Chen, Zhi-hong;Jie, Guang-Ling;Wang, Zhen;Yan, Hong-hong;Wu, Si-pei;Zhang, Shui-lian;Lu, Dan-xia;Zhang, Xu-chao;Wu, Yi-long
关键词：
NF1是一种肿瘤抑制基因，编码神经纤维蛋白并负调控Ras信号。本研究旨在探讨EGFR突变肺癌患者NF1基因的分子、临床特征及预后特征。下一代测序（NGS）用于分析广东省肺癌研究所（GLCI） 2016年6月至2020年12月肺癌患者的数据。中国肺癌患者中有4.2%（135/3220）存在体细胞NF1突变。NF1突变在老年（p < 0.001）、男性（p < 0.001）和吸烟（p < 0.001）患者中明显富集。NF1突变的患者更容易发生TP53 （p = 0.003）、BRAF （p = 0.001）和RASA1 （p = 0.026）突变，并且与EGFR突变互斥（p = 0.006）。在NF1突变（p = 0.026）或EGFR/NF1共突变（p = 0.031）肺腺癌（LUAD）患者中，TP53突变的预后较差。在有或没有NF1突变的LUAD患者中，即使在LUAD驱动基因阴性的患者中，对总生存期（OS）也没有影响。NF1/EGFR共突变患者的生存期比EGFR基因单一突变患者的生存期更长（中位生存期：47.7 m vs. 30.2 m，风险比[95% CI]， 0.47 [0.30-0.74], p = 0.004）或NF1基因（47.7 m vs. 19.0 m, 0.44 [0.27-0.73], p = 0.003）。此外，NF1突变显著延长EGFR突变/TP53野生型LUAD患者的OS (106.5 m vs. 25.5 m, 0.28 [0.13-0.59], p = 0.003)，但在EGFR/TP53共突变患者中没有（36.8 m vs. 30.2 m, 0.70 [0.39-1.26], p = 0.280）。我们的结果表明，在单中心研究中，NF1突变是EGFR突变/TP53野生型肺癌患者的良好预后因素。NF1突变患者TP53突变明显富集，OS较短。这是东亚肺癌患者中NF1基因的最大样本量分析。NF1突变肿瘤可以定义具有独特临床和分子特征的特定人群。我们的研究结果首次表明，NF1突变显著延长了EGFR突变/TP53野生型肺腺癌（LUAD）患者的总生存期，并可作为一个良好的预后因素。在NF1突变肺癌患者中TP53突变明显富集，并且在NF1突变或EGFR/NF1共突变LUAD患者中预后较差。
NF1 is a tumor suppressor gene that encodes the neurofibromin protein and negatively regulates Ras signaling. This study was aimed to investigate the molecular, clinical characteristics, and prognostic features of NF1 gene in EGFR mutant lung cancer patients. The next‐generation sequencing (NGS) was used to analyze the data from lung cancer patients in the Guangdong Lung Cancer Institute (GLCI) from June 2016 to December 2020. Somatic NF1 mutations were present in 4.2% (135/3220) of Chinese lung cancer patients. NF1 mutations where clearly enriched in older (p < 0.001), male (p < 0.001), and smoking (p < 0.001) patients. Patients with NF1 mutations were more likely to have TP53 (p = 0.003), BRAF (p = 0.001) and RASA1 (p = 0.026) mutations and mutually exclusive with EGFR mutations (p = 0.006). TP53 mutation had worsen prognosis in cases of NF1 mutant (p = 0.026) or EGFR/NF1 co‐mutant (p = 0.031) lung adenocarcinomas (LUAD) patients. There was no effect on overall survival (OS) in LUAD patients with and without NF1 mutations, even in LUAD driver‐gene negative patients. NF1/EGFR co‐mutation patients had a longer OS than a single mutation of either the EGFR gene (median OS: 47.7 m vs. 30.2 m, hazard ratio [95% CI], 0.47 [0.30–0.74], p = 0.004) or NF1 gene (47.7 m vs. 19.0 m, 0.44 [0.27–0.73], p = 0.003). Furthermore, NF1 mutations significantly prolonged OS in EGFR mutant/TP53 wild‐type LUAD patients (106.5 m vs. 25.5 m, 0.28 [0.13–0.59], p = 0.003) but not in patients with EGFR/TP53 co‐mutations (36.8 m vs. 30.2 m, 0.70 [0.39–1.26], p = 0.280). Our results indicated NF1 mutations served as a good prognostic factor in EGFR mutant/TP53 wild‐type lung cancer patients in this single‐center study. TP53 mutation was obviously enriched in NF1 mutant patients and had shorter OS. This was the largest sample size analysis for NF1 gene in East Asia lung cancer patients. NF1 mutant tumors could define a specific population with a distinct clinical and molecular profiles. Our results showed for the first time that NF1 mutations significantly prolonged overall survival in EGFR mutant/TP53 wild‐type lung adenocarcinoma (LUAD) patients and served as a good prognostic factor. TP53 mutations were clearly enriched in the NF1 mutant lung cancer patients, and had worsen prognosis in cases of NF1 mutant or EGFR/NF1 co‐mutant LUAD patients.
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影响因子：
5.2
作者：
Park JK;Kim H;Son DS;Kim NKD;Sung YK;Cho M;Lee C;Noh DH;Lee SH;Lee KT;Lee JK;Jang KT;Park WY;Lee KH
通讯作者：
Lee KH
DOI：
10.1158/1078-0432.ccr-17-2343
发表时间：
2018-03-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
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作者：
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通讯作者：
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影响因子：
64.5
作者：
CAWTHON, RM;WEISS, R;WHITE, R
通讯作者：
WHITE, R
DOI：
10.1056/nejmoa1605943
发表时间：
2016-12-29
期刊：
The New England journal of medicine
影响因子：
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作者：
Dombi E;Baldwin A;Marcus LJ;Fisher MJ;Weiss B;Kim A;Whitcomb P;Martin S;Aschbacher-Smith LE;Rizvi TA;Wu J;Ershler R;Wolters P;Therrien J;Glod J;Belasco JB;Schorry E;Brofferio A;Starosta AJ;Gillespie A;Doyle AL;Ratner N;Widemann BC
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影响因子：
4.5
作者：
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通讯作者：
Upadhyaya M