Resolving the difference between left-sided and right-sided colorectal cancer by single-cell sequencing
Wei Guo, … , Dawei Chen, Jingxin Li
Wei Guo, … , Dawei Chen, Jingxin Li
Published November 18, 2021
Citation Information: JCI Insight. 2022;7(1):e152616. https://doi.org/10.1172/jci.insight.152616.
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Research Article Gastroenterology

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

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.

Authors

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

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Figure 8

A RBP4+NTS+ cancer cell subset is unique to left-sided CRC.

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A RBP4+NTS+ cancer cell subset is unique to left-sided CRC. (A) Differen...
(A) Differences in hallmark pathway activities scored with GSVA software. Shown are t values calculated by a linear model. (B) Ligand-receptor interaction between cancer cells and TME-infiltrated cell clusters detected by CellPhoneDB 2. Selected ligand-receptor pairs are shown in the bubble plot. (C) Box plots of the expressions of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enriched differentially expressed genes of cancer cell cluster between left-sided and right-sided CRC. (D) The similarity network between cancer cell and diverse cell types in our data set. The thickness of edges in the network was denoted as the Pearson correlation coefficient between the centroids of any pair of cell types. *P < 0.05. Two-tailed paired Student’s t test was used to determine significance.