干旱区生态环境知识资源中心(Arid): Tumor Immune Microenvironment Characterization in Hepatocellular Carcinoma Identifies Four Prognostic and Immunotherapeutically Relevant Subclasses

Arid

DOI	10.3389/fonc.2020.610513
	Tumor Immune Microenvironment Characterization in Hepatocellular Carcinoma Identifies Four Prognostic and Immunotherapeutically Relevant Subclasses
	Gao, Xingxing; Huang, Hechen; Wang, Yubo; Pan, Caixu; Yin, Shengyong; Zhou, Lin; Zheng, Shusen
通讯作者	Zhou, L ; Zheng, SS (corresponding author), Zhejiang Univ, Affiliated Hosp 1, Dept Surg, Sch Med,Div Hepatobiliary & Pancreat Surg, Hangzhou, Peoples R China. ; Zhou, L ; Zheng, SS (corresponding author), NHC Key Lab Combined Multiorgan Transplantat, Hangzhou, Peoples R China. ; Zhou, L ; Zheng, SS (corresponding author), Res Ctr Diag & Treatment Hepatobiliary Dis, Key Lab Organ Transplantat, Hangzhou, Peoples R China.
来源期刊	FRONTIERS IN ONCOLOGY
ISSN	2234-943X
出版年	2021
卷号	10
英文摘要	Purpose The tumor microenvironment (TME) plays a critical role in the pathogenesis of hepatocellular carcinoma (HCC). However, underlying compositions and functions that drive the establishment and maintenance of the TME classifications are less-well understood. Methods A total of 766 HCC patients from three public cohorts were clustered into four immune-related subclasses based on 13 TME signatures (11 immune-related cells and 2 immune-related pathways) calculated by MCP-counter. After analyzing the landscapes of functional annotation, methylation, somatic mutation, and clinical characteristics, we built a TME-based Support Vector Machine of 365 patients (discovery phase) and 401 patients (validation phase). We applied this SVM model on another two independent cohorts of patients who received sorafenib/pembrolizumab treatment. Results About 33% of patients displayed an immune desert pattern. The other subclasses were different in abundance of tumor infiltrating cells. The Immunogenic subclass (17%) associated with the best prognosis presented a massive T cell infiltration and an activation of immune checkpoint pathway. The 13 TME signatures showed a good potential to predict the TME classification (average AUC = 88%). Molecular characteristics of immunohistochemistry from Zhejiang cohort supported our SVM classification. The optimum response to pembrolizumab (78%) and sorafenib (81%) was observed in patients belonging to the Immunogenic subclass. Conclusions The HCC patients from distinct immune subclass showed significant differences in clinical prognosis and response to personalized treatment. Based on tumor transcriptome data, our workflow can help to predict the clinical outcomes and to find appropriate treatment strategies for HCC patients.
英文关键词	tumor microenvironment carcinoma hepatocellular cancer immunology classification machine learning
类型	Article
语种	英语
开放获取类型	Green Published, gold
收录类别	SCI-E
WOS记录号	WOS:000625543800001
WOS类目	Oncology
WOS研究方向	Oncology
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/350320
作者单位	[Gao, Xingxing; Huang, Hechen; Wang, Yubo; Pan, Caixu; Yin, Shengyong; Zhou, Lin; Zheng, Shusen] Zhejiang Univ, Affiliated Hosp 1, Dept Surg, Sch Med,Div Hepatobiliary & Pancreat Surg, Hangzhou, Peoples R China; [Gao, Xingxing; Huang, Hechen; Wang, Yubo; Pan, Caixu; Yin, Shengyong; Zhou, Lin; Zheng, Shusen] NHC Key Lab Combined Multiorgan Transplantat, Hangzhou, Peoples R China; [Gao, Xingxing; Huang, Hechen; Wang, Yubo; Pan, Caixu; Yin, Shengyong; Zhou, Lin; Zheng, Shusen] Res Ctr Diag & Treatment Hepatobiliary Dis, Key Lab Organ Transplantat, Hangzhou, Peoples R China
推荐引用方式 GB/T 7714	Gao, Xingxing,Huang, Hechen,Wang, Yubo,et al. Tumor Immune Microenvironment Characterization in Hepatocellular Carcinoma Identifies Four Prognostic and Immunotherapeutically Relevant Subclasses[J],2021,10.
APA	Gao, Xingxing.,Huang, Hechen.,Wang, Yubo.,Pan, Caixu.,Yin, Shengyong.,...&Zheng, Shusen.(2021).Tumor Immune Microenvironment Characterization in Hepatocellular Carcinoma Identifies Four Prognostic and Immunotherapeutically Relevant Subclasses.FRONTIERS IN ONCOLOGY,10.
MLA	Gao, Xingxing,et al."Tumor Immune Microenvironment Characterization in Hepatocellular Carcinoma Identifies Four Prognostic and Immunotherapeutically Relevant Subclasses".FRONTIERS IN ONCOLOGY 10(2021).