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.

瘤内异质性 (ITH) 是癌症的一个基本特性；然而，ITH 的起源仍然知之甚少。我们对 15 名胃腺癌 (GAC) 患者的腹膜转移癌 (PC) 进行了单细胞转录组分析，构建了 45,048 个 PC 细胞的图谱，分析了肿瘤细胞群的转录组状态，深入探讨了恶性 PC 细胞的 ITH，并确定了显着的与患者生存相关。肿瘤细胞谱系/状态组成与 ITH 之间的联系在转录组学、基因型、分子和表型水平上得到了说明。我们发现了 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 的关键贡献者。ITH 的单细胞分析将 PC 标本分为两种亚型，这两种亚型在预后上独立于临床变量，并且在多个大规模 GAC 队列中推导并验证了 12 基因预后特征。预后特征似乎是 GAC 致癌和进展的基础，可用于患者分层。