Exploration of the Prognostic Value of m5C Methylation Protein NOP2 and NSUN6 in Colon Cancer

<i><b>Background:</b></i> Colorectal cancer is a prevalent malignancy with high incidence and poor prognosis. This study explores the clinical significance of 5-methylcytosine RNA modification factors, specifically the NOP2/Sun RNA Methyltransferase (NSUN) family, in colorectal cancer. <i><b>Methods:</b></i> Utilizing data from The Cancer Genome Atlas database, we analyzed the expression levels of NSUN family members in tumor tissues, their prognostic relevance, and their relationship with immune cell infiltration. To further investigate, paraffin-embedded cancer tissue microarrays were used to assess the expression of NOP2 Nucleolar Protein (NOP2) and NSUN6 in colorectal cancer tissues and adjacent normal tissues. The correlation between the expression of these genes and patient prognosis was also examined. <i><b>Results:</b></i> Bioinformatic analysis revealed that NOP2 is highly expressed in tumors, whereas NOP2/Sun RNA Methyltransferase 6 (NSUN6) is linked to poor prognosis. Immune infiltration analysis demonstrated that NOP2 expression is significantly correlated with varying levels of immune cell infiltration, including a positive association with myeloid-derived suppressor cells (MDSCs), M1 macrophages, and natural killer cells and a negative correlation with regulatory T cells and M2 macrophages. NSUN6 expression showed a significant positive correlation with MDSC infiltration. Clinical sample analysis indicated that NOP2 expression is strongly associated with tumor grade and nerve invasion, whereas NSUN6 is significantly related to nerve invasion. Survival analyses revealed that high levels of NOP2 and NSUN6 are linked to shorter overall survival. Notably, NSUN6 expression, vascular invasion, and T stage emerged as key predictors of colorectal cancer patient survival. <i><b>Conclusions:</b></i> These findings suggest that NOP2 and NSUN6 may serve as valuable molecular markers for predicting poor prognosis in colorectal cancer, with potential applications in clinical decision-making.