Role of m⁵C RNA methylation regulators in colorectal cancer prognosis and immune microenvironment

Abstract

Background RNA modification has become one of the hot topics of research as it can be used for tumor prognosis. However, its role in various biological processes is still poorly understood. The aim of this study was to investigate the role of m5C and m1A regulators on colorectal cancer prognosis using bioinformatics tools. The association between these regulators and differences in patient survival as well as the clinicopathological characteristics and tumor immune microenvironment in colorectal cancer tissues were assessed. Methods We selected publicly available colorectal cancer data sets from The Cancer Genome Atlas and used the “limma” package in R to identify differentially expressed genes. The least absolute shrinkage and selection operator regression model was used to calculate the prognostic risk, and a risk prediction model was constructed, to help assess the prognostic values of the differentially expressed genes. Finally, using TISCH and TIMER, we assessed the extent of cellular infiltration in colorectal cancer. Results We explored NSUN6 and DNMT3A expression using UALCAN and HPA and found that their expression is significantly increased in colorectal cancer tissues and correlated with sex and TP53 mutation status. Moreover, we found NSUN6 and DNMT3A were related to the infiltration of six major immune cells, with DNMT3A being closely related to dendritic cells, CD4+ T cells, and B cells, whereas NSUN6 to B cells and CD8+ T cells. Conclusion Our findings suggest that m5C regulators can predict the clinical prognostic risk and regulate the tumor immune microenvironment in colorectal cancer.

An m5C methylation regulator-associated signature predicts prognosis and therapy response in pancreatic cancer

“…NSUN6 expression could predict prognosis in both breast and colorectal cancer. However, NSUN6 expression was associated with a poor prognosis in breast cancer, and with a more favorable prognosis in colorectal cancer (Huang et al, 2021b;Fang et al, 2022). In the present study, NSUN6 expression was associated with a longer survival.…”

Optimized screening of DNA methylation sites combined with gene expression analysis to identify diagnostic markers of colorectal cancer

“…This suggests a link between methylation levels and immune cell in ltration. In colorectal cancer, DNA methyltransferase DNMT3A was found to be associated with in ltration of six major immune cells [41]. One study revealed that NEFM DNA methylation was moderately to strongly negatively associated with in ltration levels of B cells, CD8 + T cells, CD4 + T cells, macrophages, neutrophils, and dendritic cells [42].…”

m5C Regulator-mediated methylation modification clusters contribute to the immune microenvironment regulation of multiple myeloma

“…For example, cluster C was characterized by a higher number of immunocytes and immune response reactions, which included a greater abundance of plasmacytoid dendritic cells (pDCs) and interferon receptors, the former of which are increased in MM patients’ bone marrow and play a key role in the progression of MM ( Ray et al, 2015 ). Moreover, pDCs are observed in m 5 C regulators, including the DNMT3A and NSUN family, and are regulated by interferon receptors ( Bi et al, 2018 ; Fang et al, 2022 ). All three m 5 C clusters may have abundant metabolism-related pathways, which can help guide the identification of key m 5 C regulators and immune characteristics of MM.…”