摘要： 目的 探索N6-甲基腺嘌呤（m⁶A）RNA甲基化调节因子（以下简称m⁶A调节因子）与前列腺癌预后的关系。方法 从癌症基因组图谱（TCGA）数据库下载416例前列腺癌样本和80例癌旁样本的临床病理数据及其mRNA相关数据，获取METTL3、METTL14、WTAP、RBM15、ZC3H13、YTHDC1、YTHDC2、YTHDF1、YTHDF2、HNRNPC、FTO和ALKBH5共12种m⁶A调节因子。筛选出前列腺癌样本差异表达的m⁶A调节因子。对前列腺癌组织样本进行无监督聚类分组，并比较其总体生存率的差异。进行多因素Cox回归分析，根据风险评分分为高风险组和低风险组，比较2组生存率。对临床病理因素进行风险评分，构建多因素Cox回归模型，评估预后预测价值。采用免疫组织化学染色方法检测前列腺癌组织中METTL14和FTO的表达。结果 从12个m⁶A调节因子中筛选出8个差异表达的调节因子。通过无监督聚类分析将前列腺癌样本分成3组，分别为cluster 1、cluster 2和cluster 3，3组的生存时间存在显著差异。多因素Cox回归分析发现，METTL14和FTO与前列腺癌患者的预后密切相关。构建Cox回归模型，对前列腺癌患者进行风险评分，发现高、低风险组总生存率有统计学差异，且风险评分可作为独立预后指标。前列腺癌组织中METTL14和FTO蛋白阳性表达率明显高于癌旁组织（P < 0.05）。结论 本研究构建了基于m⁶A调节因子的前列腺癌预后预测模型，其中风险评分可作为独立的预后指标，METTL14和FTO可作为诊断前列腺癌的分子标志物和治疗的潜在靶点。

m⁶A RNA甲基化调节因子与前列腺癌预后的关系

刘虹汝¹, 宁静华¹, 张鑫¹, 赵严红¹, 屈润¹, 张钰哲^1,2,3

1. 大理大学基础医学院生物化学与分子生物学教研室, 云南 大理 671000;
2. 云南抗病原药用植物筛选重点实验室, 云南 大理 671000;
3. 云南省昆虫生物医药重点实验室, 云南 大理 671000

收稿日期:2023-03-27出版日期:2023-12-30发布日期:2023-12-12
通讯作者:张钰哲E-mail:lzuzyz1568@hotmail.com
作者简介:刘虹汝(1994-),女,硕士研究生
基金资助:云南省地方本科高校（部分）基础研究联合专项面上项目（202001BA070001-064，202101BA070001-102）；云南省昆虫生物医药研发重点实验室开放课题立项项目（AP2022016）：大理大学博士科研启动费立项项目（KYBS2018012）


关键词: m⁶A RNA甲基化调节因子, 前列腺癌, 预后
Abstract: Objective To explore the relationship between m⁶A RNA methylation regulators and prognosis of prostate cancer.Methods Clinicopathological and mRNA-related data of 496 cases of prostate cancer were downloaded from the Cancer Genome Atlas (TCGA) database, and 12 m⁶A regulators were identified:METTL3, METTL14, WTAP, RBM15, ZC3H13, YTHDC1, YTHDC2, YTHDF1, YTHDF2, HNRNPC, FTO, and ALKBH5. The m⁶A regulators differentially expressed in prostate cancer samples were screened. Unsupervised clustering of prostate cancer tissues was used to compare differences in overall survival. Multivariate Cox regression analysis was used to divide patients into high- and low-risk groups according to the risk scores, and survival rates were compared. The risk score of clinicopathological factors was determined, and a multivariate Cox regression analysis model was constructed to evaluate the prognostic prediction value. Immunohistochemical staining was performed to detect METTL14 and FTO expression in prostate cancer tissues.Results Eight differentially expressed regulators were screened from 12 m⁶A regulators. Unsupervised cluster analysis divided the samples into clusters 1, 2, and 3 and found significant differences in survival time in all three groups. Multivariate Cox regression analyses revealed that METTL14 and FTO were strongly associated with the prognosis of patients with prostate cancer. A Cox regression model constructed to score the risk of prostate cancer revealed that the high- and low-risk groups had survival differences, and the risk score could be used as an independent prognostic factor. The positive expression rates of METTL14 and FTO protein in prostate cancer tissues were significantly higher than those in adjacent tissues (P < 0.05).Conclusion In this study, a prognostic prediction model based on m⁶A regulators of prostate cancer was constructed, in which the risk score could be used as an independent prognostic factor. METTL14 and FTO could be used as molecular markers for the diagnosis of prostate cancer and as potential targets for treatment.
Key words: m⁶A RNA methylation regulator, prostate cancer, prognostic
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