Single-cell dissection of intratumoral heterogeneity and lineage diversity in metastatic gastric adenocarcinoma

被引:0
作者
Ruiping Wang
Minghao Dang
Kazuto Harada
Guangchun Han
Fang Wang
Melissa Pool Pizzi
Meina Zhao
Ghia Tatlonghari
Shaojun Zhang
Dapeng Hao
Yang Lu
Shuangtao Zhao
Brian D. Badgwell
Mariela Blum Murphy
Namita Shanbhag
Jeannelyn S. Estrella
Sinchita Roy-Chowdhuri
Ahmed Adel Fouad Abdelhakeem
Yuanxin Wang
Guang Peng
Samir Hanash
George A. Calin
Xingzhi Song
Yanshuo Chu
Jianhua Zhang
Mingyao Li
Ken Chen
Alexander J. Lazar
Andrew Futreal
Shumei Song
Jaffer A. Ajani
Linghua Wang
机构
[1] The University of Texas MD Anderson Cancer Center,Department of Genomic Medicine
[2] The University of Texas MD Anderson Cancer Center,Department of Gastrointestinal Medical Oncology
[3] The University of Texas MD Anderson Cancer Center,Department of Bioinformatics and Computational Biology
[4] The University of Texas MD Anderson Cancer Center,Department of Nuclear Medicine
[5] The University of Texas MD Anderson Cancer Center,Department of Surgical Oncology
[6] The University of Texas MD Anderson Cancer Center,Department of Pathology
[7] The University of Texas MD Anderson Cancer Center,Department of Clinical Cancer Prevention
[8] The University of Texas MD Anderson Cancer Center,Department of Experimental Therapeutics
[9] University of Pennsylvania School of Medicine,Department of Biostatistics and Epidemiology
[10] The University of Texas MD Anderson Cancer Center,Department of Translational Molecular Pathology
[11] The University of Texas MD Anderson Cancer Center,UTHealth Graduate School of Biomedical Sciences
[12] Kumamoto University,Department of Gastroenterological Surgery
来源
Nature Medicine | 2021年 / 27卷
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摘要
Intratumoral heterogeneity (ITH) is a fundamental property of cancer; however, the origins of ITH remain poorly understood. We performed single-cell transcriptome profiling of peritoneal carcinomatosis (PC) from 15 patients with gastric adenocarcinoma (GAC), constructed a map of 45,048 PC cells, profiled the transcriptome states of tumor cell populations, incisively explored ITH of malignant PC cells and identified significant correlates with patient survival. The links between tumor cell lineage/state compositions and ITH were illustrated at transcriptomic, genotypic, molecular and phenotypic levels. We uncovered the diversity in tumor cell lineage/state compositions in PC specimens and defined it as a key contributor to ITH. Single-cell analysis of ITH classified PC specimens into two subtypes that were prognostically independent of clinical variables, and a 12-gene prognostic signature was derived and validated in multiple large-scale GAC cohorts. The prognostic signature appears fundamental to GAC carcinogenesis and progression and could be practical for patient stratification.
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页码:141 / 151
页数:10
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