北京大学学报（医学版）2025，Vol.57Issue(4)：633-643,11.DOI:10.19723/j.issn.1671-167X.2025.04.002
氧化应激相关基因与前列腺癌关系的多组学分析
Multi-omics analysis of the relationship between oxidative stress-related gene and prostate cancer
摘要
Abstract
Objective:To investigate the relationship between oxidative stress-related genes and pros-tate cancer(PCa)from a multi-omics perspective using summary-data-based Mendelian randomization(SMR),colocalization analysis,and cellular experiments.Methods:Summary-level data on DNA methylation,gene expression,and circulating proteins were obtained and filtered.The PRACTICAL con-sortium was used as the discovery cohort,with the deCODE database serving as the validation cohort.SMR analysis and heterogeneity in dependent instruments(HEIDI)tests were conducted to assess the association and heterogeneity between oxidative stress-related genes and PCa.Colocalization analysis was performed to determine whether oxidative stress-related genes and PCa shared common causal variants.Final-ly,CCK-8 assays,wound healing assays,and Transwell invasion assays and Western blotting,were con-ducted to examine the effects of oxidative stress-related genes on the biological behavior of the PCa cell line C4-2.Results:Multi-omics analysis identified SCP2 as significantly associated with increased PCa risk across gene methylation,gene expression,and circulating protein levels.GSTP1 showed significant associations at the methylation and protein levels,while LPO was associated at the protein level.At the methylation level,SCP2 sites cg00581603(OR=1.11,95％CI:1.05-1.17)and cg13078931(OR=1.12,95％CI:1.05-1.18)were identified as pathogenic.Among the four methylation sites in GSTP1,only cg05244766(OR=0.89,95％CI:0.84-0.95)was considered protective.At the gene expression level,SCP2(OR=1.05,95％CI:1.02-1.07)was also found to be a pathogenic factor.At the circu-lating protein level,SCP2(OR=2.10,95％CI:1.34-3.29)showed a consistent pathogenic trend.In addition,GSTP1(OR=1.16,95％CI:1.07-1.25)and LPO(OR=1.12,95％CI:1.05-1.19)were significantly associated with increased PCa risk.Further functional assays demonstrated that knock-down of SCP2 significantly reduced the oncogenic phenotype of prostate cancer cells.Conclusion:Through integrated multi-omics analysis and experimental validation,this study confirmed a significant as-sociation between SCP2 and increased PCa risk.These findings enhance our understanding of PCa patho-genesis and provide new potential targets and therapeutic directions for PCa treatment.关键词
孟德尔随机化分析/前列腺肿瘤/氧化应激/多组学分析Key words
Mendelian randomization analysis/Prostatic neoplasms/Oxidative stress/Multi-omics analysis分类
医药卫生引用本文复制引用
宁家昕,王浩然,罗书航,敬吉波,王建业,侯惠民,刘明..氧化应激相关基因与前列腺癌关系的多组学分析[J].北京大学学报（医学版）,2025,57(4):633-643,11.基金项目
北京市自然科学基金(7232138)Supported by Beijing Natural Science Foundation(7232138) （7232138）
