BACKGROUND m6A-methyltransferaseMETTL3 anddemethylaseFTO regulate gene expressionby dynamically modifying RNAmethylation. However, theirclinical relevancein renal Clear Cell Carcinoma (CCRCC) hasnotbeenwell elucidated. OBJECTIVE This study aimsto investigate prognostic values of FTO and METTL3mRNA and DNA methylation, their differential expression andassociations with chemokines and inflammation-related genes in CCRCC. METHOD Kaplan-Meier survival curves and multivariate cox regression were performed for survival analyses, and random-effects meta-analysis was for differential expression of FTO and METTL3 in CCRCC. RESULTS A significantly negative correlation existed between mRNA and DNA methylation for bothFTOandMETTL3.Survival analysis showed a superior survival in patients with either high FTOmRNA or low DNA methylation,or low METTL3mRNA or high DNA methylation. The adjusted hazard ratios were 0.67 (95% CI: 0.49-0.91, p=0.01) for high vs. low FTOmRNA, 2.17 (1.38-3.42, p=0.0008) for high vs. low FTODNA methylation, 1.97 (1.45-2.68, p<0.0001) for high vs. low METTL3mRNA, and 0.49 (0.31-0.79, p=0.003) for high vs. low METTL3DNA methylation, respectively. There was a significant interaction between FTO and METTL3mRNA levels (p =0.024). Upregulation of FTO and METTL3 with 1.64 folds (95% CI: 1.43-1.89) and 1.17 folds (1.02-1.35), respectively, was observed in CCRCCvs. normal kidney tissues.FTO and METTL3mRNA had opposite direction in association with the expression of CD8+ T cell migration-relatedchemokines. CONCLUSION Dysregulated FTO and METTL3may beinvolved in the disease development and progression,and affect immune response in CCRCC.FTO and METTL3 expression and DNA methylation are potential prognostic markers of CCRCC.

中文翻译：

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肾透明细胞癌患者生存中RNA甲基化EraserFTO和作家METTL3之间的相互作用。

背景技术m6A-甲基转移酶METTL3和脱甲基酶FTO通过动态修饰RNA甲基化来调节基因表达。然而，它们在肾透明细胞癌（CCRCC）中的临床相关性尚未阐明。目的探讨CTOCC中FTO和METL3mRNA和DNA甲基化的预后价值，它们的差异表达以及与趋化因子和炎症相关基因的关联。方法采用Kaplan-Meier生存曲线和多元cox回归进行生存分析，随机效应荟萃分析用于FCRC和METTL3在CCRCC中的差异表达。结果FTO和METTL3的mRNA和DNA甲基化之间存在显着的负相关。生存分析显示，FTOmRNA高或DNA甲基化低的患者生存率更高。或低METTL3mRNA或高DNA甲基化。高FTOmRNA与低FTOmRNA的校正风险比为0.67（95％CI：0.49-0.91，p = 0.01），高FTODNA与低FTODNA甲基化的风险比为2.17（1.38-3.42，p = 0.0008），1.97（1.45-2.68，对于高与低METTL3mRNA，p <0.0001），对于高与低METTL3DNA甲基化分别为0.49（0.31-0.79，p = 0.003）。FTO和METTL3mRNA水平之间存在显着的相互作用（p = 0.024）。在CCRCCvs中，分别观察到FTO和METTL3分别上调了1.64倍（95％CI：1.43-1.89）和1.17倍（1.02-1.35）。正常肾脏组织。FTO和METTL3mRNA与CD8 + T细胞迁移相关趋化因子的表达具有相反的方向。结论FTO和METTL3失调可能与疾病的发生发展有关，并影响CCRCC的免疫反应。