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 4

Naive CD4+ T cells are predominant in right-sided CRC.

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Naive CD4+ T cells are predominant in right-sided CRC. (A) The t-SNE plo...
(A) The t-SNE plot that showed the distribution of CD4+ T cell lineages (orange, n = 4310 cells) within the atlas. CD4+ T cell populations were reclustered into 8 subclusters (color coding). (B) Annotation by left-sided and right-sided CRC cells. (C) The fraction of cells that originated from left-sided and right-sided CRC samples for 8 subgroups identified in this profile. (D) Differentiation trajectory of CD4+ T cells in CRC, with each color coded for pseudotime and clusters. (E) Monocle components were correlated with functional features of CD4+ T cells (the 4310 cells as in A), including scores of naiveness calculated by the mean expression of gene sets related to this T cell status (see Methods). (F) Kaplan-Meier survival curves of OS based on UBE2S and FAM177A1 expression using the online bioinformatics tool Kaplan-Meier Plotter. (G) The similarity network between CD4+ T 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.