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

Abstract

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.

Effect of Lactobacillus fermentum ZS40 on the NF-κB signaling pathway in an azomethane-dextran sulfate sodium-induced colon cancer mouse model

“…Moreover, studies have shown that anti-inflammatory drugs can reshape the tumor immune environment and enhance the immune blocking effect ( Pelly et al, 2021 ). Clinical studies have found that there may be a correlation between ulcerative colitis and colon cancer and that inflammatory cells are present in tumor biopsy samples ( Wang et al, 2021 ). The clinical utility of inflammation-related biomarkers in routine blood tests has been reported in a variety of cancers, and Yamamoto, T. summarizes the prognostic impact of each inflammation-related marker on CRC ( Yamamoto et al, 2021 ).…”

A Detailed Overview About the Single-Cell Analyses of Solid Tumors Focusing on Colorectal Cancer

“…These cells, compared to fibroblasts isolated from normal adjacent tissues had 76 differentially expressed genes (DEG), 5 of which ( BGN , RCN3 , TAGLN , MYL9 , and TPM2 ) were associated with poorer prognosis in the TCGA database [ 68 ]. Wang et al performed droplet-based scRNA-seq on cancerous and adjacent non-malignant inflamed tissue from a patient with ulcerative colitis-associated colon cancer [ 69 ]. They analyzed 2250 cells from tumor tissues and 2527 cells from non-malignant tissues, and classified them into cell types (myeloid cells, T cells, B cells, fibroblasts, endothelial cells, and epithelial cells) based on their transcriptional activity and further clustered them using the t-SNE method.…”

Comparison of single‑nucleus and single‑cell transcriptomes in hepatocellular carcinoma tissue

“…Advances in single-cell RNA sequencing (scRNA-seq) have revolutionized the ability to further investigate the transcriptional status of individual cells. ScRNA-seq has been successfully applied to identify cell types and understand complex subsets in various cancers, including lung ( 1 ), breast ( 2 ) and colon cancer ( 3 ). By contrast, single cells are challenging to recover entirely from certain tissues, such as brain tissue ( 4 ), and certain single cells, such as adipocytes ( 5 ), are incompatible with the droplet-based single-cell approach.…”