A Novel m7G-Related Gene Signature Predicts the Prognosis of Colon Cancer

SIMPLE SUMMARY: N7-methylguanosine (m7G) plays an important role in the tumorigenesis and progression of colon cancer (CC). According to the capability of m7G-related genes, they are classified into three types: methyltransferases, binding proteins and demethylases. Hence, m7G-related genes could promote cancers by regulating RNAs. To further explore the functions of m7G, 29 m7G-related genes were selected and then 15 of them were utilized to construct a novel signature, termed the m7G score. Altogether, we found that the prognosis of CC patients with distinct m7G scores were significantly different. Furthermore, we applied various experiments and bioinformatics analyses to validate our results. We expect that the m7G score could indicate the correct clinical situation, which might optimize our treatments for CC patients. ABSTRACT: Colon cancer (CC), one of the most common malignancies worldwide, lacks an effective prognostic prediction biomarker. N7-methylguanosine (m7G) methylation is a common RNA modification type and has been proven to influence tumorigenesis. However, the correlation between m7G-related genes and CC remains unclear. The gene expression levels and clinical information of CC patients were downloaded from public databases. Twenty-nine m7G-related genes were obtained from the published literature. Via unsupervised clustering based on the expression levels of m7G-related genes, CC patients were divided into three m7G clusters. Based on differentially expressed genes (DEGs) from the above three groups, CC patients were further divided into three gene clusters. The m7G score, a prognostic model, was established using principal component analysis (PCA) based on 15 prognosis-associated m7G genes. KM curve analysis demonstrated that the overall survival rate was remarkably higher in the high-m7G score group, which was much more significant in advanced CC patients as confirmed by subgroup analysis. Correlation analysis indicated that the m7G score was associated with tumor mutational burden (TMB), PD-L1 expression, immune infiltration, and drug sensitivity. The expression level of prognosis-related m7G genes was further confirmed in human CC cell lines and samples. This study established an m7G gene-based prognostic model (m7G score), which demonstrated the important roles of m7G-related genes during CC initiation and progression. The m7G score could be a practical biomarker to predict immunotherapy response and prognosis in CC patients.