Single-Cell Multiomics Sequencing Reveals Prevalent Genomic Alterations in Tumor Stromal Cells of Human Colorectal Cancer

Copyright © 2020 Elsevier Inc. All rights reserved..

To what extent stromal cells in the tumor microenvironment (TME) are transformed by colorectal cancer (CRC) cells is unexplored. To dissect alterations in these non-malignant cells, we performed single-cell multiomics sequencing of 21 patients with microsatellite-stable CRCs and 6 cancer-free, elderly individuals. Surprisingly, somatic copy number alterations (SCNAs) are prevalent in immune cells, fibroblasts, and endothelial cells in both the TME and the normal tissues of each individual. Moreover, the proportions of fibroblasts with SCNAs in tumors (11.1%-47.7%) are much higher than those in adjacent normal tissues (1.1%-10.6%), with gain of chromosome 7 strongly enriched in the TME, clearly indicating clonal expansion. Furthermore, five genes (BGN, RCN3, TAGLN, MYL9, and TPM2) are identified as fibroblast-specific biomarkers of poorer prognosis of CRC. Our study provides evidence and functional relevance of pervasive genomic alterations in the stromal cells of TME in CRC.

Errataetall:

CommentIn: Nat Rev Cancer. 2021 Jan;21(1):3. - PMID 33177706

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:38

Enthalten in:

Cancer cell - 38(2020), 6 vom: 14. Dez., Seite 818-828.e5

Sprache:

Englisch

Beteiligte Personen:

Zhou, Yuan [VerfasserIn]
Bian, Shuhui [VerfasserIn]
Zhou, Xin [VerfasserIn]
Cui, Yueli [VerfasserIn]
Wang, Wendong [VerfasserIn]
Wen, Lu [VerfasserIn]
Guo, Limei [VerfasserIn]
Fu, Wei [VerfasserIn]
Tang, Fuchou [VerfasserIn]

Links:

Volltext

Themen:

BGN protein, human
Biglycan
Biomarkers, Tumor
Calcium-Binding Proteins
Colorectal cancer
Journal Article
MYL9 protein, human
Microfilament Proteins
Muscle Proteins
Myosin Light Chains
RCN3 protein, human
Research Support, Non-U.S. Gov't
Somatic copy number alterations
Stromal cell
TPM2 protein, human
Transgelin
Tropomyosin
Tumor microenvironment

Anmerkungen:

Date Completed 26.05.2021

Date Revised 27.05.2021

published: Print-Electronic

CommentIn: Nat Rev Cancer. 2021 Jan;21(1):3. - PMID 33177706

Citation Status MEDLINE

doi:

10.1016/j.ccell.2020.09.015

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM316648884