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
Wei Guo, Cuiyu Zhang, Xia Wang, Dandan Dou, Dawei Chen, Jingxin Li
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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 5

Right-sided CRC occupies a large proportion of highly migratory exhausted CD8+ T cells.

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Right-sided CRC occupies a large proportion of highly migratory exhauste...
(A) The t-SNE plot that showed the distribution of CD8+ T cell lineages (orange, n = 2351 cells) within the atlas. CD8+ T cell populations were reclustered into 7 subclusters (color coding). (B) Annotation by left-sided and right-sided CRC cells. (C) Z score normalized mean expression of selected T cell function–associated genes in each cell cluster. Black boxes highlight the prominent patterns defining known T cell subtypes. (D) The fraction of cells that originated from left-sided and right-sided CRC samples for 7 subgroups identified in this profile. (E) Differentiation trajectory of CD8+ T cells in CRC, with each color coded for pseudotime and clusters. (F) Monocle components were correlated with functional features of CD8+ T cells (the 2351 cells as in A), including scores of exhaustion and cytotoxicity calculated by the mean expression of gene sets related to T cell status. (G) Box plots of the expressions of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and coinhibition program of all CD4+ and CD8+ T cell clusters between left-sided and right-sided CRC. *P < 0.05; Two-tailed paired Student’s t test was used to determine significance.