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

Adenocarcinoma / genetics Adult Aged Cell Lineage / genetics Chromosomes, Human, Pair 17 / genetics Cohort Studies DNA Copy Number Variations Female Gene Expression Profiling Genetic Variation Humans Male Middle Aged Peritoneal Neoplasms / genetics Prognosis RNA-Seq Single-Cell Analysis Stomach Neoplasms / genetics

Journal

Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015

Informations de publication

Date de publication:
01 2021
Historique:
received: 04 08 2019
accepted: 09 10 2020
pubmed: 6 1 2021
medline: 23 1 2021
entrez: 5 1 2021
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1038/s41591-020-1125-8 PMID: 33398161 PMC: PMC8074162
pubmed: 33398161
doi: 10.1038/s41591-020-1125-8
pii: 10.1038/s41591-020-1125-8
pmc: PMC8074162
mid: NIHMS1688918
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

141-151

Subventions

Organisme : NCI NIH HHS
ID : R01 CA160433
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NIH HHS
ID : S10 OD024977
Pays : United States
Organisme : U.S. Department of Defense (United States Department of Defense)
ID : CA150334
Pays : International
Organisme : U.S. Department of Defense (United States Department of Defense)
ID : CA160433
Pays : International
Organisme : U.S. Department of Defense (United States Department of Defense)
ID : CA170906
Pays : International
Organisme : U.S. Department of Defense (United States Department of Defense)
ID : CA160445
Pays : International

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Auteurs

Ruiping Wang (R)

Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Minghao Dang (M)

Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Kazuto Harada (K)

Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Gastroenterological Surgery, Kumamoto University, Kumamoto, Japan.
ORCID: 0000-0001-5818-7072

Guangchun Han (G)

Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
ORCID: 0000-0001-9277-2507

Fang Wang (F)

Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Melissa Pool Pizzi (M)

Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Meina Zhao (M)

Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Ghia Tatlonghari (G)

Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Shaojun Zhang (S)

Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
ORCID: 0000-0001-5760-5797

Dapeng Hao (D)

Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Yang Lu (Y)

Department of Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
ORCID: 0000-0001-9571-4679

Shuangtao Zhao (S)

Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Brian D Badgwell (BD)

Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Mariela Blum Murphy (M)

Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Namita Shanbhag (N)

Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Jeannelyn S Estrella (JS)

Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Sinchita Roy-Chowdhuri (S)

Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Ahmed Adel Fouad Abdelhakeem (AAF)

Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Yuanxin Wang (Y)

Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Guang Peng (G)

Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
ORCID: 0000-0002-4392-1497

Samir Hanash (S)

Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
ORCID: 0000-0002-4210-1593

George A Calin (GA)

Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
ORCID: 0000-0002-7427-0578

Xingzhi Song (X)

Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Yanshuo Chu (Y)

Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Jianhua Zhang (J)

Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
ORCID: 0000-0001-5412-9860

Mingyao Li (M)

Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
ORCID: 0000-0001-8180-0621

Ken Chen (K)

Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
ORCID: 0000-0003-4013-5279

Alexander J Lazar (AJ)

Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
ORCID: 0000-0002-6395-4499

Andrew Futreal (A)

Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
ORCID: 0000-0001-8663-2671

Shumei Song (S)

Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
ORCID: 0000-0002-8128-6287

Jaffer A Ajani (JA)

Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. jajani@mdanderson.org.
ORCID: 0000-0001-9946-0629

Linghua Wang (L)

Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. LWang22@mdanderson.org.
UTHealth Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. LWang22@mdanderson.org.
ORCID: 0000-0001-9380-0266

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Classifications MeSH

questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs épithéliales épidermoïdes et glandulaires › Carcinomes › Adénocarcinome › Single-cell dissection of intratumoral...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Single-cell dissection of intratumoral...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Single-cell dissection of intratumoral...
questionsmedicales.fr › Phénomènes physiologiques des appareils urinaire et reproducteur › Phénomènes physiologiques de la reproduction › Reproduction › Développement embryonnaire et foetal › Développement embryonnaire › Lignage cellulaire › Single-cell dissection of intratumoral...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Chromosomes › Chromosomes de mammifère › Chromosomes humains › Chromosomes humains 16-18 › Chromosomes humains de la paire 17 › Single-cell dissection of intratumoral...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Single-cell dissection of intratumoral...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Variation structurale du génome › Variations de nombre de copies de segment d'ADN › Single-cell dissection of intratumoral...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de profil d'expression de gènes › Single-cell dissection of intratumoral...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Single-cell dissection of intratumoral...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Single-cell dissection of intratumoral...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Single-cell dissection of intratumoral...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies du péritoine › Tumeurs du péritoine › Single-cell dissection of intratumoral...
questionsmedicales.fr › Diagnostic › Pronostic › Single-cell dissection of intratumoral...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ARN › RNA-Seq › Single-cell dissection of intratumoral...
questionsmedicales.fr › Techniques d'investigation › Techniques cytologiques › Analyse sur cellule unique › Single-cell dissection of intratumoral...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies gastro-intestinales › Maladies de l'estomac › Tumeurs de l'estomac › Single-cell dissection of intratumoral...