Identification of the relationship between single-cell N6-methyladenosine regulators and the infiltrating immune cells in esophageal carcinoma.

BACKGROUND

N6-methyladenosine (mA) RNA methylation plays a crucial role in important genomic processes in a variety of malignancies. However, the characterization of mA with infiltrating immune cells in the tumor microenvironment (TME) in esophageal squamous carcinoma (ESCC) remains unknown.

METHODS

The single-cell transcriptome data from five ESCC patients in our hospital were analyzed, and TME clusters associated with prognosis and immune checkpoint genes were investigated. Cell isolation and qPCR were conducted to validate the gene characterization in different cells.

RESULTS

According to distinct biological processes and marker genes, macrophages, T cells, and B cells clustered into three to four different subgroups. In addition, we demonstrated that mA RNA methylation regulators were strongly related to the clinical and biological features of ESCC. Analysis of transcriptome data revealed that mA-mediated TME cell subsets had high predictive value and showed a close relationship with immune checkpoint genes. The validation results from qPCR demonstrated the characteristics of essential genes. CellChat analysis revealed that RNA from TME cells mA methylation-associated cell subtypes had substantial and diversified interactions with cancer cells. Further investigation revealed that MIF- (CD74+CXCR4) and MIF- (CD74CD44) ligand-receptor pairings facilitated communication between mA-associated subtypes of TME cells and cancer cells.

CONCLUSION

Overall, our study demonstrated for the first time the function of mA methylation-mediated intercellular communication in the microenvironment of tumors in controlling tumor development and anti-tumor immune regulation in ESCC.