小柯机器人

美国德克萨斯大学MD安德森癌症中心Linghua Wang和Jaffer A. Ajani团队合作在研究中取得进展。他们提出转移性胃腺癌肿瘤内异质性（ITH）和谱系多样性的单细胞解剖。相关论文于2021年1月4日发表在《自然-医学》杂志上。

他们对15例胃腺癌（GAC）患者的腹膜癌（PC）进行了单细胞转录组谱分析，绘制了45,048个PC细胞图谱，分析了肿瘤细胞群的转录组状态，仔细研究了恶性PC细胞的ITH并发现了重要的与患者生存率相关。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。他们发现了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的关键因素。

ITH的单细胞分析将PC标本分为两个亚型，它们在预后上与临床变量无关，并且在多个大规模GAC队列中得出并验证了12基因的预后标记。预后标志似乎是GAC癌变和进展的基础，对患者分层可能是实用的。

研究人员表示，ITH是癌症的基本特性。但是，ITH的起源仍然知之甚少。

附：英文原文

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

Author: 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

Issue&Volume: 2021-01-04

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. Single-cell analysis of gastric cancer samples tracks the cell of origin of metastatic lesions and identifies an independent prognostic signature of the clinical outcome.

DOI: 10.1038/s41591-020-1125-8

Source: https://www.nature.com/articles/s41591-020-1125-8

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