DNA甲基化修饰调节剂介导的前列腺癌分子簇与肿瘤代谢特征

DNA Methylation Modification Regulator-Mediated Molecular Clusters and Tumor Metabolic Characterization in Prostate Cancer.

作者信息

Zhang Yanlong, Liang Xuezhi, Zhang Liyun, Wang Dongwen

机构信息

Department of Urology, First Hospital of Shanxi Medical University, Taiyuan, China.

Shanxi Medical University, Taiyuan, China.

出版信息

J Oncol. 2021 Nov 11;2021:2408637. doi: 10.1155/2021/2408637. eCollection 2021.

DOI:10.1155/2021/2408637

PMID:34804158

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8601836/

Abstract

BACKGROUND

An increasing number of studies have indicated a close link between DNA methylation and tumor metabolism. However, the overall influence of DNA methylation on tumor metabolic characteristics in prostate cancer (PCa) remains unclear.

METHODS

We first explored the subtypes of DNA methylation modification regulators and tumor metabolic features of 1,205 PCa samples using clustering analysis and gene set variation analysis based on the mRNA levels of DNA methylation modification regulators. A DNA methylation-related score (DMS) was calculated using principal component analysis and the DNA methylation modification-related gene signatures to quantify DNA methylation characteristics. We then performed a meta-analysis to identify the hazard ratio of DMS in the six cohorts. In addition, a nomogram was drawn using univariate and multivariate Cox analyses based on the DMS and clinical variables. Finally, a drug sensitivity analysis of the DMS was performed based on the genomics of drug sensitivity in cancer datasets.

RESULTS

Three PCa clusters showing different DNA methylation modification patterns and tumor metabolic features were identified. A DMS system was established to quantify the characteristics of DNA methylation modification. PCa samples showed a differential metabolic landscape between the high and low DMS groups. The prognostic value of the DMS and nomogram was independently validated in multiple cohorts. A high DMS was associated with increases in the tumor mutation burden, copy number variation, and microsatellite instability; high tumor heterogeneity; and poor prognosis. Finally, DMS was closely related to different types of antitumor treatment.

CONCLUSION

Improving the understanding of tumor metabolism by characterizing DNA methylation modification patterns and using the DMS may help clinicians predict prognosis and aid in more personalized antitumor therapy strategies for PCa.

摘要

背景

越来越多的研究表明DNA甲基化与肿瘤代谢之间存在密切联系。然而，DNA甲基化对前列腺癌（PCa）肿瘤代谢特征的总体影响仍不清楚。

方法

我们首先基于DNA甲基化修饰调节因子的mRNA水平，使用聚类分析和基因集变异分析，探索了1205例PCa样本的DNA甲基化修饰调节因子亚型和肿瘤代谢特征。使用主成分分析和DNA甲基化修饰相关基因特征计算DNA甲基化相关评分（DMS），以量化DNA甲基化特征。然后，我们进行了一项荟萃分析，以确定六个队列中DMS的风险比。此外，基于DMS和临床变量，使用单变量和多变量Cox分析绘制了列线图。最后，基于癌症数据集的药物敏感性基因组学对DMS进行了药物敏感性分析。

结果

识别出三个显示不同DNA甲基化修饰模式和肿瘤代谢特征的PCa簇。建立了一个DMS系统来量化DNA甲基化修饰的特征。PCa样本在高DMS组和低DMS组之间表现出不同的代谢格局。DMS和列线图的预后价值在多个队列中得到了独立验证。高DMS与肿瘤突变负担、拷贝数变异和微卫星不稳定性增加、高肿瘤异质性以及预后不良相关。最后，DMS与不同类型的抗肿瘤治疗密切相关。