Gene Signatures and Prognostic Values of m6A Genes in Nasopharyngeal Carcinoma

Shanshan Lu; Zhengzheng Yu; Zhiqiang Xiao; Yiya Zhang

doi:10.3389/fonc.2020.00875

Gene Signatures and Prognostic Values of m⁶A Genes in Nasopharyngeal Carcinoma

Front Oncol. 2020 Jun 11:10:875. doi: 10.3389/fonc.2020.00875. eCollection 2020.

Authors

Shanshan Lu^{1

2

3}, Zhengzheng Yu^{1

2}, Zhiqiang Xiao^{1

2}, Yiya Zhang^{3

4}

Affiliations

¹ Research Center of Carcinogenesis and Targeted Therapy, Xiangya Hospital, Central South University, Changsha, China.
² The Higher Educational Key Laboratory for Cancer Proteomics and Translational Medicine of Hunan Province, Xiangya Hospital, Central South University, Changsha, China.
³ National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
⁴ Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.

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.

Keywords: METTL3; immune infiltration; m6A; nasopharyngeal carcinoma; prognostic factors.