Genomic Profiling and Prognostic Value Analysis of Genetic Alterations in Chinese Resected Lung Cancer With Invasive Mucinous Adenocarcinoma

doi:10.3389/fonc.2020.603671

	Genomic Profiling and Prognostic Value Analysis of Genetic Alterations in Chinese Resected Lung Cancer With Invasive Mucinous Adenocarcinoma
	Cai, Lei 2,3; Wang, Jiangfeng 2,3; Yan, Junrong 1; Zeng, Jian 2,3; Zhu, Liang 3,4; Liang, Jinxiao 2,3; Pan, Chao 2,3; Huang, Xiancong 2,3; Jin, Ju 3,4; Xu, Yang 1
刊名	FRONTIERS IN ONCOLOGY
	2021-01-11
卷号	10
关键词	invasive mucinous adenocarcinoma surgical resection next generation sequencing genomic profiling prognostic biomarker
ISSN号	2234-943X
DOI	10.3389/fonc.2020.603671
通讯作者	Jiang, Youhua(jiangyh@zjcc.org.cn)
英文摘要	Background Invasive mucinous adenocarcinoma (IMA) of the lung is a distinct histological subtype with unique clinical and pathological features. Despite previous genomic studies on lung IMA, the genetic characteristics and the prognosis-related biomarkers in Chinese surgically resected lung IMA remain unclear. Methods We collected 76 surgically resected primary tumors of invasive lung adenocarcinoma, including 51 IMA and 25 non-mucinous adenocarcinomas (non-IMA). IMA was further divided into pure-IMA (mucinous features >= 90%) and mixed-IMA subgroups. Comprehensive genomic profiling based on targeted next-generation sequencing (NGS) of 425 genes was explored and genomic characteristics were evaluated for the correlation with postoperative disease-free survival (DFS). Results IMA had a unique genetic profile, with more diverse driver mutations and more tumor drivers/suppressors co-occurrence than that of non-IMA. The frequency of EGFR (72.0% vs. 40.0% vs. 23.1%, p=0.002) and ALK (undetected vs. 20.0% vs. 26.9%, p=0.015) alterations showed a trend of gradual decrease and increase from non-IMA to mixed-IMA to pure-IMA, respectively. The frequency of KRAS mutations in pure-IMA was higher than that in mixed-IMA, albeit statistically insignificant (23.1% vs. 4.0%, p=0.10). TP53 mutation was significantly less in pure-IMA compared to mixed-IMA and non-IMA (23.1% vs. 52.0% vs. 56.0%, p=0.03). Besides, IMA exhibited less arm-level amplifications (p=0.04) and more arm-level deletions (p=0.004) than non-IMA, and the frequency of amplification and deletion also showed a trend of gradual decrease and increase from non-IMA to mixed-IMA to pure-IMA, respectively. Furthermore, prognosis analysis in stage III IMA patients showed that patients harboring alterations in EGFR (mDFS=30.3 vs. 16.0 months, HR=0.19, P=0.027) and PI3K pathway (mDFS=36.0 vs. 16.0 months, HR=0.12, P=0.023) achieved prolonged DFS, while patients with poorly differentiated tumors (mDFS=14.1 vs. 28.0 months, HR=3.75, p=0.037) or with KRAS mutations (mDFS=13.0 vs. 20.0 months, HR=6.95, p=0.027) had shorter DFS. Multivariate analysis showed that KRAS mutations, PI3K pathway alterations, and tumor differentiation status were independent factors that have statistically significant influences on clinical outcomes of IMA patients. Conclusion Our study provided genomic insights into Chinese surgically resected lung IMA. We also identified several genomic features that may serve as potential biomarkers on postoperative recurrence in IMA patients with stage III disease.
资助项目	National Natural Science Foundation of China[81802995] ; National Natural Science Foundation of China[81702851] ; Medical Science and Technology Project of Zhejiang Province[2018KY024]
WOS关键词	EGFR MUTATION ; OPEN-LABEL ; DRIVER MUTATIONS ; KRAS MUTATIONS ; SMOKERS VARIES ; CHEMOTHERAPY ; CRIZOTINIB ; SURVIVAL ; RET ; DISCOVERY
WOS研究方向	Oncology
语种	英语
出版者	FRONTIERS MEDIA SA
WOS记录号	WOS:000611140600001
资助机构	National Natural Science Foundation of China ; Medical Science and Technology Project of Zhejiang Province
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/119832]
专题	中国科学院合肥物质科学研究院
通讯作者	Jiang, Youhua
作者单位	1.Nanjing Geneseeq Technol Inc, Dept Med, Nanjing, Peoples R China 2.Univ Chinese Acad Sci, Zhejiang Canc Hosp, Canc Hosp, Dept Thorac Surg, Hangzhou, Peoples R China 3.Chinese Acad Sci, Inst Canc & Basic Med IBMC, Hangzhou, Peoples R China 4.Univ Chinese Acad Sci, Zhejiang Canc Hosp, Canc Hosp, Dept Pathol, Hangzhou, Peoples R China 5.Tradit Chinese Med Hosp Huzhou, Dept Med Oncol, Huzhou, Peoples R China 6.Zhejiang Univ, Affiliated Hosp 1, Haining Branch, Dept Med Oncol,Haining Peoples Hosp, Haining, Peoples R China
推荐引用方式 GB/T 7714	Cai, Lei,Wang, Jiangfeng,Yan, Junrong,et al. Genomic Profiling and Prognostic Value Analysis of Genetic Alterations in Chinese Resected Lung Cancer With Invasive Mucinous Adenocarcinoma[J]. FRONTIERS IN ONCOLOGY,2021,10.
APA	Cai, Lei.,Wang, Jiangfeng.,Yan, Junrong.,Zeng, Jian.,Zhu, Liang.,...&Jiang, Youhua.(2021).Genomic Profiling and Prognostic Value Analysis of Genetic Alterations in Chinese Resected Lung Cancer With Invasive Mucinous Adenocarcinoma.FRONTIERS IN ONCOLOGY,10.
MLA	Cai, Lei,et al."Genomic Profiling and Prognostic Value Analysis of Genetic Alterations in Chinese Resected Lung Cancer With Invasive Mucinous Adenocarcinoma".FRONTIERS IN ONCOLOGY 10(2021).