Single-cell dissection of the multicellular ecosystem and molecular features underlying microvascular invasion in hepatocellular carcinoma

doi:10.1097/HEP.0000000000000673

科研成果详情

题名	Single-cell dissection of the multicellular ecosystem and molecular features underlying microvascular invasion in hepatocellular carcinoma
作者	Li, Ke 1,2; Zhang, Rui 1,3; Wen, Fukai 1,3; Zhao, Yunzheng 1,3; Meng, Fanshuai 1,3; Li, Qingyu 1,3; Hao, Aimin 1; Yang, Bailu 1; Lu, Zhaoyang 1,3; Cui, Yifeng 1,3; Zhou, Meng2
发表日期	2023-11-16
发表期刊	HEPATOLOGY 影响因子和分区
语种	英语
原始文献类型	Article ; Early Access
关键词	microvascular invasion hepatocellular carcinoma single-cell RNA sequencing tumor microenvironment
其他关键词	GROWTH-FACTOR ; LANDSCAPE
摘要	Background and aims: Microvascular invasion (MVI) is a crucial pathological hallmark of hepatocellular carcinoma (HCC), intricately associated with poor outcomes, early recurrence and intrahepatic metastasis following surgical resection and transplantation. However, the intricate tumor microenvironment (TME) and transcriptional programs underlying MVI in HCC remain poorly understood.Approach and results: We performed single-cell RNA sequencing of 46,789 individual cells from 10 samples of MVI+ (MVI present) and MVI- (MVI absent) HCC patients. We conducted comprehensive and comparative analyses to characterize cellular and molecular features associated with MVI, and validated key findings using external bulk, single-cell and spatial transcriptomic datasets, coupled with multiplex immunofluorescence assays. The comparison identified specific subtypes of immune and stromal cells critical to the formation of the immunosuppressive and pro-metastatic microenvironment in MVI+ tumors, including cycling T cells, LAMP3+ dendritic cells, TREM2+ macrophages, myofibroblasts, and arterial i endothelial cells. MVI+ malignant cells are characterized by high proliferation rates while MVI-malignant cells exhibit an inflammatory milieu. Additionally, we identified the MDK-dominated interaction between TREM2+ macrophages and malignant cells as a contributor to MVI formation and tumor progression. Notably, we unveiled a spatially co-located multicellular community exerting a dominant role in shaping the immunosuppressive microenvironment of MVI and correlating with unfavorable prognosis.Conclusions: This study provides a comprehensive single-cell atlas of MVI in HCC, shedding light on the complex multicellular ecosystem and molecular features associated with MVI. These findings deepen our understanding of the underlying mechanisms driving MVI and provide valuable insights for improving clinical diagnosis and developing more effective treatment strategies.
资助项目	National Natural Scientific Foundation of China [62372331, 81972230]; Heilongjiang Province key research and development plan project [2022ZX06C17]; Heilongjiang Postdoctoral Science Foundation [LBH-Z20178]; Scientific Foundation of the First Affiliated Hospital of Harbin Medical University [2021B03]; Excellent Youth Science Fund of the First Affiliated Hospital of Harbin Medical University [2021Y01]; Chen Xiaoping Foundation for the Development of Science and Technology of Hubei Province [CXPJJH122002-092]
出版者	LIPPINCOTT WILLIAMS & WILKINS
ISSN	0270-9139
EISSN	1527-3350
卷号	79 期号:6 页码:1293-1309
DOI	10.1097/HEP.0000000000000673
页数	32
WOS类目	Gastroenterology & Hepatology
WOS研究方向	Gastroenterology & Hepatology
WOS记录号	WOS:001111359100001
收录类别	SCIE ; PUBMED ; SCOPUS
在线发表日期	2023-11
URL	查看原文
PubMed ID	37972953
SCOPUSEID	2-s2.0-85183058506
通讯作者地址	[Lu, Zhaoyang]Department of Hepatic Surgery,The First Affiliated Hospital of Harbin Medical University,Harbin,150007,China ; [Cui, Yifeng]Department of Hepatic Surgery,The First Affiliated Hospital of Harbin Medical University,Harbin,150007,China ; [Zhou, Meng]School of Biomedical Engineering,Wenzhou Medical University,Wenzhou,325027,China
Scopus学科分类	Hepatology
TOP期刊	TOP期刊
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/185717
专题	仁济学院_眼视光、生物医学工程学部眼视光学院（生物医学工程学院）、附属眼视光医院_生物医学信息系
通讯作者	Lu, Zhaoyang; Cui, Yifeng; Zhou, Meng
作者单位	1.Department of Hepatic Surgery,The First Affiliated Hospital of Harbin Medical University,Harbin,China; 2.School of Biomedical Engineering,Wenzhou Medical University,Wenzhou,China; 3.Key Laboratory of Hepatosplenic Surgery,Ministry of Education,The First Affiliated Hospital of Harbin Medical University,Harbin,China
第一作者单位	仁济学院_眼视光、生物医学工程学部
通讯作者单位	仁济学院_眼视光、生物医学工程学部
推荐引用方式 GB/T 7714	Li, Ke,Zhang, Rui,Wen, Fukai,et al. Single-cell dissection of the multicellular ecosystem and molecular features underlying microvascular invasion in hepatocellular carcinoma[J]. HEPATOLOGY,2023,79(6):1293-1309.
APA	Li, Ke., Zhang, Rui., Wen, Fukai., Zhao, Yunzheng., Meng, Fanshuai., ... & Zhou, Meng. (2023). Single-cell dissection of the multicellular ecosystem and molecular features underlying microvascular invasion in hepatocellular carcinoma. HEPATOLOGY, 79(6), 1293-1309.
MLA	Li, Ke,et al."Single-cell dissection of the multicellular ecosystem and molecular features underlying microvascular invasion in hepatocellular carcinoma".HEPATOLOGY 79.6(2023):1293-1309.