Evidence map›Paper›PMID 35773407›Full record

ArticleNature genetics2022

Single-cell and bulk transcriptome sequencing identifies two epithelial tumor cell states and refines the consensus molecular classification of colorectal cancer.

Ignasius Joanito, Pratyaksha Wirapati, Nancy Zhao, Zahid Nawaz, Grace Yeo, Fiona Lee, Christine L P Eng, Dominique Camat Macalinao, Merve Kahraman, Harini Srinivasan and 43 more

Abstract read
In one paragraph

Article in Nature genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 284 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
284citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

284 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  5. Single-cell epigenomics of colorectal cancer.Experimental & molecular medicine · 2026
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224 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

53 authors.

Ignasius JoanitoGenome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.ORCID http://orcid.org/0000-0001-9623-4706
Pratyaksha Wirapati *Bioinformatics Core Facility, Swiss Institute of Bioinformatics, Lausanne, Switzerland.ORCID http://orcid.org/0000-0002-0327-4686
Nancy Zhao *Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.ORCID http://orcid.org/0000-0001-6217-854X
Zahid Nawaz *Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.ORCID http://orcid.org/0000-0002-4972-0637
Grace YeoGenome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.ORCID http://orcid.org/0000-0002-8920-8208
Fiona LeeGenome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.ORCID http://orcid.org/0000-0002-9092-1932
Christine L P EngGenome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
Dominique Camat MacalinaoNational Cancer Centre, Singapore, Singapore.
Merve KahramanGenome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
Harini SrinivasanGenome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
Vairavan LakshmananNational Cancer Centre, Singapore, Singapore.
Sara VerbandtMolecular Digestive Oncology, Department of Oncology, Katholieke Universiteit Leuven, Leuven, Belgium.
Petros TsantoulisHôpitaux Universitaires de Genève, Geneva, Switzerland.ORCID http://orcid.org/0000-0003-3613-6682
Nicole GunnNational Cancer Centre, Singapore, Singapore.
Prasanna Nori VenkateshGenome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.ORCID http://orcid.org/0000-0002-3974-6200
Zhong Wee PohGenome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
Rahul NaharMSD International GmbH (Singapore Branch), Singapore, Singapore.
Hsueh Ling Janice OhMSD International GmbH (Singapore Branch), Singapore, Singapore.
Jia Min LooGenome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.ORCID http://orcid.org/0000-0002-6605-4031
Shumei ChiaGenome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
Lih Feng CheowNational University of Singapore, Singapore, Singapore.
Elsie CherubaNational University of Singapore, Singapore, Singapore.ORCID http://orcid.org/0000-0002-5289-0434
Michael Thomas WongMSD International GmbH (Singapore Branch), Singapore, Singapore.
Lindsay KuaNational Cancer Centre, Singapore, Singapore.ORCID http://orcid.org/0000-0002-4975-3084
Clarinda ChuaNational Cancer Centre, Singapore, Singapore.
Andy NguyenNantOmics, Rockville, MD, USA.ORCID http://orcid.org/0000-0003-1329-1006
Justin GolovanNantOmics, Rockville, MD, USA.
Anna GanGenome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
Wan-Jun LimNational Cancer Centre, Singapore, Singapore.
Yu Amanda GuoGenome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.ORCID http://orcid.org/0000-0003-3478-7991
Choon Kong YapGenome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
Brenda TayNational Cancer Centre, Singapore, Singapore.
Yourae HongSamsung Genome Institute, Samsung Medical Center, Seoul, Korea.ORCID http://orcid.org/0000-0001-6683-433X
Dawn Qingqing ChongNational Cancer Centre, Singapore, Singapore.
Aik-Yong ChokDepartment of Colorectal Surgery, Singapore General Hospital, Singapore, Singapore.
Woong-Yang ParkSamsung Genome Institute, Samsung Medical Center, Seoul, Korea.
Shuting HanNational Cancer Centre, Singapore, Singapore.
Mei Huan ChangDepartment of Colorectal Surgery, Singapore General Hospital, Singapore, Singapore.
Isaac Seow-EnDepartment of Colorectal Surgery, Singapore General Hospital, Singapore, Singapore.ORCID http://orcid.org/0000-0001-8287-6812
Cherylin FuDepartment of Colorectal Surgery, Singapore General Hospital, Singapore, Singapore.
Ronnie MathewDepartment of Colorectal Surgery, Singapore General Hospital, Singapore, Singapore.
Ee-Lin TohDepartment of Colorectal Surgery, Singapore General Hospital, Singapore, Singapore.ORCID http://orcid.org/0000-0002-9739-6691
Lewis Z HongMSD International GmbH (Singapore Branch), Singapore, Singapore.ORCID http://orcid.org/0000-0002-1971-8149
Anders Jacobsen SkanderupGenome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.ORCID http://orcid.org/0000-0001-6847-4980
Ramanuj DasGuptaGenome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.ORCID http://orcid.org/0000-0001-9015-3729
Chin-Ann Johnny OngDepartment of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore.
Kiat Hon LimDepartment of Anatomical Pathology, Singapore General Hospital, Singapore, Singapore.
Emile K W TanDepartment of Colorectal Surgery, Singapore General Hospital, Singapore, Singapore.
Si-Lin KooNational Cancer Centre, Singapore, Singapore.
Wei Qiang LeowDepartment of Anatomical Pathology, Singapore General Hospital, Singapore, Singapore.
Sabine TejparMolecular Digestive Oncology, Department of Oncology, Katholieke Universiteit Leuven, Leuven, Belgium. sabine.tejpar@uzleuven.be.ORCID http://orcid.org/0000-0003-3281-8643
Shyam PrabhakarGenome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore. prabhakars@gis.a-star.edu.sg.ORCID http://orcid.org/0000-0002-6409-0661
Iain Beehuat TanGenome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore. iain.tan.b.h@singhealth.com.sg.ORCID http://orcid.org/0000-0003-4951-0354

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The consensus molecular subtype (CMS) classification of colorectal cancer is based on bulk transcriptomics. The underlying epithelial cell diversity remains unclear. We analyzed 373,058 single-cell transcriptomes from 63 patients, focusing on 49,155 epithelial cells. We identified a pervasive genetic and transcriptomic dichotomy of malignant cells, based on distinct gene expression, DNA copy number and gene regulatory network. We recapitulated these subtypes in bulk transcriptomes from 3,614 patients. The two intrinsic subtypes, iCMS2 and iCMS3, refine CMS. iCMS3 comprises microsatellite unstable (MSI-H) cancers and one-third of microsatellite-stable (MSS) tumors. iCMS3 MSS cancers are transcriptomically more similar to MSI-H cancers than to other MSS cancers. CMS4 cancers had either iCMS2 or iCMS3 epithelium; the latter had the worst prognosis. We defined the intrinsic epithelial axis of colorectal cancer and propose a refined 'IMF' classification with five subtypes, combining intrinsic epithelial subtype (I), microsatellite instability status (M) and fibrosis (F).

Indexed as

Colorectal NeoplasmsNeoplasms, Glandular and EpithelialEpithelial CellsHumansMicrosatellite InstabilityMicrosatellite RepeatsTranscriptome

Identifiers

PMID35773407
PMCPMC9279158

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.