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 9

Heterogeneity of macrophages in the TME of CRC.

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Heterogeneity of macrophages in the TME of CRC. (A) Relative expression ...
(A) Relative expression of Mrc1 and CD14, APOE, and PTGS2 overlaid on t-SNE plot. Summary expression of 3 resident biomarkers (Mrc1, Itgax, and CD163) and 3 recruited biomarkers (Cd14, Apoe, and Mafb), M1 markers and M2 markers overlaid on t-SNE plot. (B and C) Bubble plot comparing expression of resident (blue) and recruited (red) biomarkers, M2 (blue) and M1 (red) markers across M1-like or M2-like macrophage clusters from left-sided or right-sided CRC. (D) Mean normalized expression of genes annotated for enriched pathways of M1-like and M2-like macrophage cluster from left-sided and right-sided CRC. (E) Violin plots display the distribution of expression of M1 and M2 polarization signature genes between left-sided and right-sided CRC. (F) Heatmap of positive immune checkpoint expression on macrophages. The row Z score was implicated to represent the expression level. *P < 0.05; **P < 0.01; ***P < 0.001. Two-tailed paired Student’s t test was used to determine significance.