Landscape of cell heterogeneity and evolutionary trajectory in ulcerative colitis-associated colon cancer revealed by single-cell RNA sequencing

OBJECTIVE: The goal of this study was to get preliminary insight on the intra-tumor heterogeneity in colitis-associated cancer (CAC) and to reveal a potential evolutionary trajectory from ulcerative colitis (UC) to CAC at the single-cell level. METHODS: Fresh samples of tumor tissues and adjacent UC tissues from a CAC patient with pT3N1M0 stage cancer were examined by single-cell RNA sequencing (scRNA-seq). Data from The Cancer Genome Atlas (TCGA) and The Human Protein Atlas were used to confirm the different expression levels in normal and tumor tissues and to determine their relationships with patient prognosis. RESULTS: Ultimately, 4,777 single-cell transcriptomes (1,220 genes per cell) were examined, of which 2,250 (47%) and 2,527 (53%) originated from tumor and adjacent UC tissues, respectively. We defined the composition of cancer-associated stromal cells and identified six cell clusters, including myeloid, T and B cells, fibroblasts, endothelial and epithelial cells. Notable pathways and transcription factors involved in these cell clusters were analyzed and described. Moreover, the precise cellular composition and developmental trajectory from UC to UC-associated colon cancer were graphed, and it was predicted that CD74, CLCA1, and DPEP1 played a potential role in disease progression. CONCLUSIONS: scRNA-seq technology revealed intra-tumor cell heterogeneity in UC-associated colon cancer, and might provide a promising direction to identify novel potential therapeutic targets in the evolution from UC to CAC.