Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Nat Med. 2021 Jan;27(1):141-151. doi: 10.1038/s41591-020-1125-8. Epub 2021 Jan 4.
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.
肿瘤内异质性（ITH）是癌症的一个基本特征；然而，其起源仍知之甚少。我们对 15 名胃腺癌（GAC）患者的腹膜癌病（PC）进行了单细胞转录组谱分析，构建了 45048 个 PC 细胞图谱，分析了肿瘤细胞群体的转录组状态，深入探讨了恶性 PC 细胞的 ITH，并确定了与患者生存显著相关的因素。在转录组、基因型、分子和表型水平上说明了肿瘤细胞谱系/状态组成与 ITH 之间的联系。我们揭示了 PC 标本中肿瘤细胞谱系/状态组成的多样性，并将其定义为 ITH 的主要贡献者。对 ITH 的单细胞分析将 PC 标本分为两种亚型，这两种亚型与临床变量无关，并且在多个大型 GAC 队列中衍生和验证了一个 12 基因预后特征。该预后特征似乎对 GAC 发生和进展具有基础性，并且对患者分层可能具有实际意义。
