Lu Shanshan, Yu Zhengzheng, Xiao Zhiqiang, Zhang Yiya
Research Center of Carcinogenesis and Targeted Therapy, Xiangya Hospital, Central South University, Changsha, China.
The Higher Educational Key Laboratory for Cancer Proteomics and Translational Medicine of Hunan Province, Xiangya Hospital, Central South University, Changsha, China.
Front Oncol. 2020 Jun 11;10:875. doi: 10.3389/fonc.2020.00875. eCollection 2020.
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 (mA) is closely related to tumorigenesis. However, the relationship between mA-related genes and prognosis of NPC is poorly understood. Our research aims to discover the prognostic value of mA RNA methylation genes in NPC. In this study, we analyzed the differentially expressed mA-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 mA 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 mA modification in NPC, providing novel insight into NPC prognosis and therapeutic strategies.
鼻咽癌（NPC）是一种局部侵袭率高且早期易发生远处转移的恶性肿瘤。越来越多的研究表明，N6-甲基腺嘌呤甲基化（mA）与肿瘤发生密切相关。然而，mA相关基因与NPC预后之间的关系尚不清楚。我们的研究旨在发现mA RNA甲基化基因在NPC中的预后价值。在本研究中，我们分析了NPC样本与正常对照样本之间差异表达的mA相关基因，发现在GSE68799和GSE53819中，有两个上调基因（YTHDF3和IGF2BP2）和一个下调基因（METTL3）存在重叠。接下来，我们发现NPC患者中IGF2BP1高表达以及METTL3和YTHDF3低表达提示无进展生存期（PFS）较差。随后，对这四个mA基因进行共识聚类分析并建立风险模型。使用三个基因（GF2BP1 + IGF2BP2 + METTL3）的风险特征是一个独立的预后因素，并可预测NPC的临床病理特征。此外，基因本体（GO）、京都基因与基因组百科全书（KEGG）分析以及CIBERSORT算法显示，该风险特征与NPC中的免疫浸润密切相关。最后，使用免疫组织化学技术成功验证了METTL3在NPC组织中的表达及临床意义。总之，我们的研究结果揭示了mA修饰在NPC中的潜在作用，为NPC的预后和治疗策略提供了新的见解。
