Single-cell dissection of intratumoral heterogeneity and lineage diversity in metastatic gastric adenocarcinoma
Menée à partir d'échantillons d'ascites péritonéales prélevés sur 15 patients atteints d'un adénocarcinome gastrique, cette étude analyse le profil transcriptomique de plus de 45 000 métastases péritonéales, examine la contribution de la diversité des lignées cellulaires dans l'hétérogénéité intratumorale et identifie une signature, basée sur l'expression de 12 gènes, permettant d'établir un pronostic
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.
Nature Medicine , résumé, 2021