甲基转移酶样蛋白3与前列腺癌患者预后的相关性

Association between methyltransferase-like 3 and prognosis in patients with prostate cancer

目的探讨甲基转移酶样蛋白3(METTL3)与前列腺癌(PCa)患者预后的相关性,以期建立新的预测PCa患者预后的方法。方法使用开放数据集和PCa组织芯片评估METTL3基因和蛋白的表达、METTL3与Gleason评分(GS)之间的相关性以及METTL3预测PCa不良预后的能力,构建列线图模型定量评估PCa预后。结果与正常前列腺组织比较,PCa组织中METTL3基因和蛋白表达水平显著升高(P<0.05)。METTL3在高危PCa组(GS>7分)中的基因和蛋白表达水平明显高于中-低危PCa组(GS≤7分)(P<0.05)。METTL3基因高表达组患者的短期和长期无进展生存率和总体生存率均较METTL3基因低表达组患者差(P<0.05)。此外,本研究建立了一个由7个受METTL3 N6-甲基腺嘌呤(m6A)修饰调控的靶基因组成的风险模型。该风险模型中的7个靶基因主要与细胞周期过程密切相关,METTL3蛋白表达水平与细胞周期蛋白B1(CCNB1)的蛋白表达水平呈显著正相关(r=0.30,P=0.0025)。结论METTL3具有预测PCa预后的潜力,其可能通过m6A修饰调控与细胞周期过程密切相关的靶基因的表达来影响PCa预后。

Objective To explore the association between methyltransferase-like 3(METTL3)and prostate cancer(PCa)prognosis,so as to establish a novel prognostic prediction model for PCa.Methods Public datasets and PCa tissue microarray were used to evaluate the gene and protein expressions of METTL3,the association between METTL3 and Gleason score(GS),and the ability of METTL3 to predict poor outcomes of PCa.A nomogram was constructed to quantitatively evaluate the prognosis of PCa.Results The gene and protein expressions of METTL3 were significantly upregulated in PCa tissues compared to normal tissues(P<0.05).Moreover,the expressions of METTL3 were significantly higher in high-risk PCa tissues(GS>7)compared to low-moderate risk PCa tissues(GS≤7)(P<0.05).Patients with elevated expressions of METTL3 exhibited poorer short-term and long-term progression-free and overall survival outcomes when compared to those with lower expressions of METTL3(P<0.05).In addition,a risk model composed of 7 target genes regulated by METTL3 N6-methyladenine(m6A)modification was established.The 7 target genes were closely associated with the cell cycle process.The protein expression of METTL3 exhibited a significant positive correlation with the protein expression of cell cycle protein B1(CCNB1)(r=0.30,P=0.0025).Conclusion METTL3 exhibits the potential as a prognostic predictor for PCa,which may affect PCa prognosis through the regulation of the expressions of target genes closely associated with the cell cycle process via m6A modification.