Genomic and transcriptomic profiling indicates the prognosis significance of mutational signature for TMB-high subtype in Chinese patients with gastric cancer

doi:10.1016/j.jare.2022.10.019

	Genomic and transcriptomic profiling indicates the prognosis significance of mutational signature for TMB-high subtype in Chinese patients with gastric cancer
	Cheng, Yanan 1,2; Bu, Dechao 3; Zhang, Qiaoling 1,2; Sun, Rebecca 4; Lyle, Stephen 4; Zhao, Gang 5; Dong, Li 1,2; Li, Hui 5; Zhao, Yi 3,6; Yu, Jinpu 1,2,7; Hao, Xishan 1,2,7
	2023-09-01
发表期刊	JOURNAL OF ADVANCED RESEARCH
ISSN	2090-1232
卷号	51 页码:121-134
摘要	Introduction: Gastric cancer (GC)is the third leading cause of cancer-related deaths in China and immunotherapy emerging as a revolutionary treatment for GC recently. Tumor mutational burden (TMB) is a predictive biomarker of immunotherapy in multiple cancers. However, the prognostic signif-icance and subtype of TMB in GC is not fully understood.Objectives: This study aims to evaluate the prognostic value of TMB in Chinese GC and further classify TMB-high GC (GCTMB-H) patients combing with mutational signatures.Methods: Genomic profiling of 435 cancer-gene panel was performed using 206 GC samples from Chinese people. Actionable genetic alterations were compared across all the samples to generate actionable sub typing. The prognostic value of TMB in Chinese GC was evaluated. Mutational signatures were analyzed on TMB-H subtype to stratify the prognosis of TMB. Transcriptomic analysis was applied to compare the distributed immunocytes among different subtypes. Results: 88.3% (182/206) of GC samples had at least one mutation, while 45.1% (93/206) had at least one somatic copy number alteration (SCNA). 29.6% (61/206) of GC samples were TMB-H, including 13 MSI-H and 48 MSS tumors. According to distinct genetic alteration profiles of 69 actionable genes, we classified GC samples into eight molecular subtypes, including TMB-H, ERBB2 amplified, ATM mutated, BRCA2 mutated, CDKN2A/B deleted, PI3KCA mutated, KRAS mutated, and less-mutated subtype. TMB-H subtype presented a remarkable immune-activated phenotype as determined by transcriptomic analysis that was further validated in the TCGA GC cohort. GCTMB-H patients exhibited significantly better survival (P = 0.047). But Signature 1-high GCTMB-H patients had relatively worse prognosis (P = 0.0209, HR = 2.571) than Signature 1-low GCTMB-H patients from Chinese GC cohort, also validated in TCGA GC cohort, presenting highly activated carbohydrate, fatty acid or lipid metabolism.Conclusion: The Signature 1-high GCTMB-H could be a marker of poor prognosis and is associated with metabolism disorder.(c) 2023 The Authors. Published by Elsevier B.V. on behalf of Cairo University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
关键词	Gastric cancer Comprehensive genomic profiling TMB Mutational signature Tumor metabolism
DOI	10.1016/j.jare.2022.10.019
收录类别	SCI
语种	英语
资助项目	National Science and Technology Support Program of China[2015BAI12B15] ; National Science and Technology Support Program of China[2018ZX09201015] ; National Natural Science Foundation of China[82072588] ; National Natural Science Foundation of China[82002601] ; National Natural Science Foundation of China[81872143] ; National Natural Science Foundation of China[81702280] ; National Key Research and Development Program of China: The Net construction of human genetic resource Bio-bank in North China[2016YFC1201703] ; Projects of Science and Technology of Tianjin[13ZCZCSY20300] ; Projects of Science and Technology of Tianjin[18JCQNJC82700] ; Tianjin Key Medical Discipline (Specialty) Construction Project[TJYXZDXK-009A] ; Innovation Fund, Institute of Computing, CAS[E161080]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:001075780800001
出版者	ELSEVIER
引用统计	被引频次：21[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://119.78.100.204/handle/2XEOYT63/21150
专题	中国科学院计算技术研究所期刊论文_英文
通讯作者	Zhao, Yi; Yu, Jinpu; Hao, Xishan
作者单位	1.Tianjin Med Univ Canc Inst & Hosp, Key Lab Canc Immunol & Biotherapy, Key Lab Canc Prevent & Therapy, Canc Mol Diagnost Core, Tianjin, Peoples R China 2.Natl Clin Res Ctr Canc, Tianjins Clin Res Ctr Canc, Tianjin, Peoples R China 3.Chinese Acad Sci, Res Ctr Ubiquitous Comp Syst, Adv Comp Res Ctr, Key Lab Intelligent Informat Proc,Inst Comp Techno, Beijing, Peoples R China 4.KEW Inc, 303 Wyman St, Waltham, MA USA 5.Tianjin Med Univ Canc Inst & Hosp, Dept Gastrointestinal Canc Biol, Tianjin, Peoples R China 6.Chinese Acad Sci, Inst Comp Technol, 6 Kexueyuan South Rd Zhongguancun, Beijing 100190, Peoples R China 7.Tianjin Med Univ Canc Inst & Hosp, Huanhuxi Rd, Tianjin 300060, Peoples R China
推荐引用方式 GB/T 7714	Cheng, Yanan,Bu, Dechao,Zhang, Qiaoling,et al. Genomic and transcriptomic profiling indicates the prognosis significance of mutational signature for TMB-high subtype in Chinese patients with gastric cancer[J]. JOURNAL OF ADVANCED RESEARCH,2023,51:121-134.
APA	Cheng, Yanan.,Bu, Dechao.,Zhang, Qiaoling.,Sun, Rebecca.,Lyle, Stephen.,...&Hao, Xishan.(2023).Genomic and transcriptomic profiling indicates the prognosis significance of mutational signature for TMB-high subtype in Chinese patients with gastric cancer.JOURNAL OF ADVANCED RESEARCH,51,121-134.
MLA	Cheng, Yanan,et al."Genomic and transcriptomic profiling indicates the prognosis significance of mutational signature for TMB-high subtype in Chinese patients with gastric cancer".JOURNAL OF ADVANCED RESEARCH 51(2023):121-134.