| Literature DB >> 33398161 |
Ruiping Wang1, Minghao Dang1, Kazuto Harada2,3, Guangchun Han1, Fang Wang4, Melissa Pool Pizzi2, Meina Zhao2, Ghia Tatlonghari2, Shaojun Zhang1, Dapeng Hao1, Yang Lu5, Shuangtao Zhao1, Brian D Badgwell6, Mariela Blum Murphy2, Namita Shanbhag2, Jeannelyn S Estrella7, Sinchita Roy-Chowdhuri7, Ahmed Adel Fouad Abdelhakeem2, Yuanxin Wang1, Guang Peng8, Samir Hanash8, George A Calin9, Xingzhi Song1, Yanshuo Chu1, Jianhua Zhang1, Mingyao Li10, Ken Chen4, Alexander J Lazar7,11, Andrew Futreal1, Shumei Song2, Jaffer A Ajani12, Linghua Wang13,14.
Abstract
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.Entities:
Mesh:
Year: 2021 PMID: 33398161 PMCID: PMC8074162 DOI: 10.1038/s41591-020-1125-8
Source DB: PubMed Journal: Nat Med ISSN: 1078-8956 Impact factor: 53.440