Resolving the difference between left-sided and right-sided colorectal cancer by single-cell sequencing

Wei Guo; Cuiyu Zhang; Xia Wang; Dandan Dou; Dawei Chen; Jingxin Li

doi:10.1172/jci.insight.152616

Resolving the difference between left-sided and right-sided colorectal cancer by single-cell sequencing

JCI Insight. 2022 Jan 11;7(1):e152616. doi: 10.1172/jci.insight.152616.

Authors

Wei Guo¹, Cuiyu Zhang², Xia Wang², Dandan Dou², Dawei Chen³, Jingxin Li²

Affiliations

¹ Department of Colorectal Surgery, Shandong University Qilu Hospital, Jinan, Shandong, China.
² Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
³ Laboratory of Medical Chemistry, Interdisciplinary Cluster for Applied Genoproteomics (GIGA) Stem Cells, University of Liege, CHU de Liège, Sart-Tilman, Liege, Belgium.

Abstract

Colorectal cancers (CRCs) exhibit differences in incidence, pathogenesis, molecular pathways, and outcome depending on the location of the tumor. The transcriptomes of 27,927 single human CRC cells from 3 left-sided and 3 right-sided CRC patients were profiled by single-cell RNA-Seq (scRNA-Seq). Right-sided CRC harbors a significant proportion of exhausted CD8+ T cells of a highly migratory nature. One cluster of cells from left-sided CRC exhibiting states preceding exhaustion and a high ratio of preexhausted/exhausted T cells were favorable prognostic markers. Notably, we identified a potentially novel RBP4+NTS+ subpopulation of cancer cells that exclusively expands in left-sided CRC. Tregs from left-sided CRC showed higher levels of immunotherapy-related genes than those from right-sided CRC, indicating that left-sided CRC may have increased responsiveness to immunotherapy. Antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC) induced by M2-like macrophages were more pronounced in left-sided CRC and correlated with a good prognosis in CRC.

Keywords: Cancer; Gastroenterology.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Colorectal Neoplasms* / classification
Colorectal Neoplasms* / genetics
Colorectal Neoplasms* / metabolism
Colorectal Neoplasms* / pathology
Humans
RNA-Seq / methods*
Single-Cell Analysis / methods*
Transcriptome / genetics*

Grants and funding

This work was supported in part by the National Natural Science Foundation of China (82000779, 31971061).