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.

引用

页码：141 / 151

页数：10

共 104 条

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