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.
Highlights
Often grouped as one disease, right-sided colon cancer and left-sided colon cancer represent clinically distinct entities with significant differences in their prognosis and treatment outcomes[1, 2]
We noticed that several cell clusters were enriched in both left-sided and right-sided Colorectal cancers (CRCs) (Figures 1C). 13,488 single cells originated from left-sided CRC, while 14,439 originated from right-sided CRC (Figure 1C)
Mast cells from right-sided CRC accounted for 71.5% of all cluster 13 cells, while left-sided CRC only accounted for 28.5% (Figure 2C)
Summary
Often grouped as one disease, right-sided colon cancer (originating from cecum, ascending colon, hepatic flexure) and left-sided colon cancer (originating from splenic flexure, descending colon, sigmoid colon) represent clinically distinct entities with significant differences in their prognosis and treatment outcomes[1, 2]. The full spectrum of distinct cell types and their molecular characteristics remain to be well defined in left-sided and right-sided malignant colorectal lesions, which hampers our ability to investigate their differences in colorectal cancer (CRC) pathogenesis. We performed a scRNA-seq survey of 27,927 cells from 6 samples obtained during curative surgery for three left-sided CRCs and three right-sided CRCs, and constructed a single-cell transcriptome atlas for malignant colorectal lesions.
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