Nature medicine · 2021
Single-cell dissection of intratumoral heterogeneity and lineage diversity in metastatic gastric adenocarcinoma.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАПоддержка службы здравоохранения СШАНазвание и аннотация: Перевод пока не подготовлен
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Wang Ruiping, Dang Minghao, Harada Kazuto, Han Guangchun, Wang Fang, Pool Pizzi Melissa, Zhao Meina, Tatlonghari Ghia, Zhang Shaojun, Hao Dapeng, Lu Yang, Zhao Shuangtao, Badgwell Brian D, Blum Murphy Mariela, Shanbhag Namita, Estrella Jeannelyn S, Roy-Chowdhuri Sinchita, Abdelhakeem Ahmed Adel Fouad, Wang Yuanxin, Peng Guang, Hanash Samir, Calin George A, Song Xingzhi, Chu Yanshuo, Zhang Jianhua, Li Mingyao, Chen Ken, Lazar Alexander J, Futreal Andrew, Song Shumei, Ajani Jaffer A, Wang Linghua
Аннотация
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.