Gene Signatures and Prognostic Values of m(6)A Genes in Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma (NPC) is a malignant tumor with a high rate of local invasion and early distant metastasis. Accumulating studies suggest that N6-methyladenosine methylation (m(6)A) is closely related to tumorigenesis. However, the relationship between m(6)A-related genes and prognosis of NPC is poorly understood. Our research aims to discover the prognostic value of m(6)A RNA methylation genes in NPC. In this study, we analyzed the differentially expressed m(6)A-related genes between NPC samples and normal control samples and found that two upregulated genes (YTHDF3 and IGF2BP2) and one downregulated gene (METTL3) were overlapped in GSE68799 and GSE53819. Next, we found that high expression of IGF2BP1 and low expression of METTL3 and YTHDF3 in NPC patients showed poor progression-free survival (PFS). Subsequently, the four m(6)A genes were selected for consensus cluster analysis, and risk models were established. The risk signature, using three genes (GF2BP1 + IGF2BP2 + METTL3), was an independent prognostic factor and predicts the clinicopathological features of NPC. Additionally, the GO, KEGG analysis, and CIBERSORT algorithm revealed that the risk signature was closely associated to immune infiltration in NPC. Finally, the expression and clinical significance of METTL3 were successfully validated in NPC tissues using immunohistochemical techniques. In conclusion, our finding revealed the potential role of m(6)A modification in NPC, providing novel insight into NPC prognosis and therapeutic strategies.