Abstract
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 (m6A) is closely related to tumorigenesis. However, the relationship between m6A-related genes and prognosis of NPC is poorly understood. Our research aims to discover the prognostic value of m6A RNA methylation genes in NPC. In this study, we analyzed the differentially expressed m6A-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 m6A 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 m6A modification in NPC, providing novel insight into NPC prognosis and therapeutic strategies.
Highlights
Nasopharyngeal carcinoma (NPC), which occurs in squamous epithelial cells of the nasopharyngeal mucosa [1], has a high prevalence [2] in central and southern coastal areas of China and Southeast Asian countries [3, 4]
The results showed that high expression of IGF2BP1 and low expression of METTL3 and YTHDF3 showed poor progression-free survival (PFS) in NPC patients (Figures 1C–E and Figure S1)
Previous studies have shown that the progression of NPC is regulated by epitranscriptomics [33, 34]. m6A is the most common and plentiful modification in post-transcriptional modification of RNA, but so far, little is known about the role of m6A in NPC
Summary
Nasopharyngeal carcinoma (NPC), which occurs in squamous epithelial cells of the nasopharyngeal mucosa [1], has a high prevalence [2] in central and southern coastal areas of China and Southeast Asian countries [3, 4]. Methyltransferase catalyzes m6A methylation of RNA, and its core members are METTL3, METTL14, WTAP, etc. Demethylase mediates m6A demethylation modification, with core members FTO and ALKBH5 [17]. Binding proteins recognize RNA methylation modifications, including the YTHDF family (YTHDF1/2/3), nuclear heterogeneous riboprotein family (HNRNPA2B1, HNRNPC), and eukaryotic initiation factor (eIF) [15, 16]. M6A methylation is involved in RNA metabolism-related processes such as RNA transcription, processing, splicing, degradation, and translation [18, 19]. A recent study revealed that the dysregulated m6A-related genes are involved in the progression of various cancers [20]. Immunohistochemical analysis (IHC) was used to detect the expression of m6A-related genes in NPC tissues to determine the prognostic biomarkers of NPC
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