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

Autor: Wang R; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Dang M; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Harada K; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.; Department of Gastroenterological Surgery, Kumamoto University, Kumamoto, Japan., Han G; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Wang F; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Pool Pizzi M; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Zhao M; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Tatlonghari G; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Zhang S; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Hao D; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Lu Y; Department of Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Zhao S; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Badgwell BD; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Blum Murphy M; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Shanbhag N; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Estrella JS; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Roy-Chowdhuri S; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Abdelhakeem AAF; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Wang Y; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Peng G; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Hanash S; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Calin GA; Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Song X; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Chu Y; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Zhang J; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Li M; Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA., Chen K; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Lazar AJ; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Futreal A; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Song S; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Ajani JA; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. jajani@mdanderson.org., Wang L; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. LWang22@mdanderson.org.; UTHealth Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. LWang22@mdanderson.org.
Jazyk: angličtina
Zdroj: Nature medicine [Nat Med] 2021 Jan; Vol. 27 (1), pp. 141-151. Date of Electronic Publication: 2021 Jan 04.
DOI: 10.1038/s41591-020-1125-8
Abstrakt: 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.
Databáze: MEDLINE
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