全基因组甲基化关联研究鉴定了非洲裔美国男性前列腺癌中差异甲基化的基因。

Epigenome-wide association study of prostate cancer in African American men identified differentially methylated genes.

机构信息

Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.

Department of Radiation Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.

出版信息

Cancer Med. 2024 Aug;13(16):e70044. doi: 10.1002/cam4.70044.

DOI:10.1002/cam4.70044

PMID:39162297

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11334050/

Abstract

INTRODUCTION

Men with African ancestry have the highest incidence and mortality rates of prostate cancer (PCa) worldwide.

METHODS

This study aimed to identify differentially methylated genes between tumor vs. adjacent normal and aggressive vs. indolent PCa in 121 African American patients. Epigenome-wide DNA methylation patterns in tumor DNA were assessed using the human Illumina Methylation EPIC V1 array.

RESULTS

Around 5,139 differentially methylated CpG-sites (q < 0.01, lΔβl > 0.2) were identified when comparing normal vs. tumor, with an overall trend of hypermethylation in prostate tumors. Multiple representative differentially methylated regions (DMRs), including immune-related genes, such as CD40, Galectin3, OX40L, and STING, were detected in prostate tumors when compared to adjacent normal tissues. Based on an epigenetic clock model, we observed that tumors' total number of stem cell divisions and the stem cell division rate were significantly higher than adjacent normal tissues. Regarding PCa aggressiveness, 2,061 differentially methylated CpG-sites (q < 0.05, lΔβl > .05) were identified when the grade group (GG)1 was compared with GG4/5. Among these 2,061 CpG sites, 155 probes were consistently significant in more than one comparison. Among these genes, several immune system genes, such as COL18A1, S100A2, ITGA4, HLA-C, and ADCYAP1, have previously been linked to tumor progression in PCa.

CONCLUSION

Several differentially methylated genes involved in immune-oncologic pathways associated with disease risk or aggressiveness were identified. In addition, 261 African American-specific differentially methylated genes related to the risk of PCa were identified. These results can shedlight on potential mechanisms contributing to PCa disparities in the African American Population.

摘要

引言

非洲裔男性的前列腺癌（PCa）发病率和死亡率在全球范围内最高。

方法

本研究旨在鉴定 121 名非裔美国患者肿瘤与相邻正常组织以及侵袭性与惰性 PCa 之间的差异甲基化基因。使用人类 Illumina Methylation EPIC V1 阵列评估肿瘤 DNA 中的全基因组 DNA 甲基化模式。

结果

在正常组织与肿瘤组织的比较中，发现了约 5139 个差异甲基化 CpG 位点（q<0.01，lΔβl>0.2），前列腺肿瘤呈总体超甲基化趋势。与相邻正常组织相比，在前列腺肿瘤中检测到多个代表性差异甲基化区域（DMR），包括免疫相关基因，如 CD40、Galectin3、OX40L 和 STING。基于表观遗传时钟模型，我们观察到肿瘤的总干细胞分裂数和干细胞分裂率明显高于相邻正常组织。关于 PCa 的侵袭性，当比较等级组（GG）1 与 GG4/5 时，发现了 2061 个差异甲基化 CpG 位点（q<0.05，lΔβl>0.05）。在这 2061 个 CpG 位点中，有 155 个探针在不止一个比较中始终显著。在这些基因中，一些免疫系统基因，如 COL18A1、S100A2、ITGA4、HLA-C 和 ADCYAP1，先前已被证明与 PCa 中的肿瘤进展有关。