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

Joanito, I.; Wirapati, P.; Zhao, N.; Nawaz, Z.; Yeo, G.; Lee, F.; Eng, CLP; Macalinao, D.C.; Kahraman, M.; Srinivasan, H.; Lakshmanan, V.; Verbandt, S.; Tsantoulis, P.; Gunn, N.; Venkatesh, P.N.; Poh, Z.W.; Nahar, R.; Oh, HLJ; Loo, J.M.; Chia, S.; Cheow, L.F.; Cheruba, E.; Wong, M.T.; Kua, L.; Chua, C.; Nguyen, A.; Golovan, J.; Gan, A.; Lim, W.J.; Guo, Y.A.; Yap, C.K.; Tay, B.; Hong, Y.; Chong, D.Q.; Chok, A.Y.; Park, W.Y.; Han, S.; Chang, M.H.; Seow-En, I.; Fu, C.; Mathew, R.; Toh, E.L.; Hong, L.Z.; Skanderup, A.J.; DasGupta, R.; Ong, C.J.; Lim, K.H.; Tan, EKW; Koo, S.L.; Leow, W.Q.; Tejpar, S.; Prabhakar, S.; Tan, I.B.

doi:10.1038/s41588-022-01100-4

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

Details

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License: CC BY 4.0

Serval ID

serval:BIB_27A9BBA898C9

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

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

Journal

Nature genetics

Author(s)

Joanito I., Wirapati P., Zhao N., Nawaz Z., Yeo G., Lee F., Eng CLP, Macalinao D.C., Kahraman M., Srinivasan H., Lakshmanan V., Verbandt S., Tsantoulis P., Gunn N., Venkatesh P.N., Poh Z.W., Nahar R., Oh HLJ, Loo J.M., Chia S., Cheow L.F., Cheruba E., Wong M.T., Kua L., Chua C., Nguyen A., Golovan J., Gan A., Lim W.J., Guo Y.A., Yap C.K., Tay B., Hong Y., Chong D.Q., Chok A.Y., Park W.Y., Han S., Chang M.H., Seow-En I., Fu C., Mathew R., Toh E.L., Hong L.Z., Skanderup A.J., DasGupta R., Ong C.J., Lim K.H., Tan EKW, Koo S.L., Leow W.Q., Tejpar S., Prabhakar S., Tan I.B.

ISSN

1546-1718 (Electronic)

ISSN-L

1061-4036

Publication state

Published

Issued date

07/2022

Peer-reviewed

Oui

Volume

Number

Pages

963-975

Language

english

Notes

Publication types: Journal Article
Publication Status: ppublish

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).

Keywords

Colorectal Neoplasms/genetics, Colorectal Neoplasms/pathology, Epithelial Cells/pathology, Humans, Microsatellite Instability, Microsatellite Repeats/genetics, Neoplasms, Glandular and Epithelial/genetics, Transcriptome/genetics

URN

urn:nbn:ch:serval-BIB_27A9BBA898C96

OAI-PMH

oai:serval.unil.ch:BIB_27A9BBA898C9

DOI

10.1038/s41588-022-01100-4

Pubmed

35773407

Web of science

000819274500001

Open Access

Yes