Prognostic Significance of EZH2-Related Gene Variants in Patients With Prostate Cancer Undergoing Androgen Deprivation Therapy.

IF 2.6 4区 医学 Q2 GENETICS & HEREDITY
Shu-Pin Huang, Bo-Ying Bao, Ta-Hsien Chuang, Chao-Yuan Huang, Chia-Cheng Yu, Victor C Lin, Te-Ling Lu, Yei-Tsung Chen
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Abstract

Background/aim: Prostate cancer remains a major global health burden, with treatment resistance posing a significant challenge. Enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2), a histone methyltransferase, is frequently overexpressed in prostate cancer, contributing to tumor progression and castration resistance. Clinical trials of EZH2 inhibitors may have therapeutic benefits. This study aimed to evaluate the impact of genetic variants in EZH2-related genes on survival outcomes in prostate cancer.

Patients and methods: We conducted a genetic association study evaluating 76 single nucleotide polymorphisms (SNPs) across 10 EZH2-related genes in 630 patients with prostate cancer undergoing androgen deprivation therapy (ADT). Functional analyses, including gene ontology and pathway enrichment assessments, were performed to elucidate the biological significance of key genes across multiple datasets.

Results: DNMT3A rs77993651 was significantly associated with both cancer-specific survival [hazard ratio (HR)=0.82, p=0.042] and overall survival (HR=0.80, p=0.011). Functional annotation indicated that rs77993651 resides within enhancer histone marks, potentially regulating DNMT3A expression. Elevated DNMT3A expression was observed in prostate tumor tissues and correlated with more aggressive features and shorter progression-free survival. Gene set enrichment analysis revealed that DNMT3A expression was strongly associated with cell cycle G2/M checkpoint regulation, implicating a role in prostate cancer progression.

Conclusion: The prognostic significance of DNMT3A and its genetic variant rs77993651 in prostate cancer is herein highlighted. Targeting DNMT3A-mediated pathways may offer novel therapeutic strategies for prostate cancer management.

ezh2相关基因变异在雄激素剥夺治疗前列腺癌患者中的预后意义
背景/目的:前列腺癌仍然是全球主要的健康负担,治疗耐药性构成重大挑战。zeste 2多梳抑制复合体2亚基增强子(EZH2)是一种组蛋白甲基转移酶,在前列腺癌中经常过度表达,有助于肿瘤进展和去势抵抗。EZH2抑制剂的临床试验可能具有治疗益处。本研究旨在评估ezh2相关基因的遗传变异对前列腺癌患者生存结局的影响。患者和方法:我们进行了一项遗传关联研究,评估了630例接受雄激素剥夺治疗(ADT)的前列腺癌患者中10个ezh2相关基因的76个单核苷酸多态性(snp)。功能分析,包括基因本体和途径富集评估,通过多个数据集阐明关键基因的生物学意义。结果:DNMT3A rs77993651与肿瘤特异性生存[危险比(HR)=0.82, p=0.042]和总生存(HR=0.80, p=0.011)均显著相关。功能注释表明rs77993651位于增强子组蛋白标记中,可能调节DNMT3A的表达。在前列腺肿瘤组织中观察到DNMT3A表达升高,并与更具侵袭性的特征和更短的无进展生存期相关。基因集富集分析显示,DNMT3A表达与细胞周期G2/M检查点调节密切相关,暗示在前列腺癌进展中起作用。结论:本文强调DNMT3A及其基因变异rs77993651在前列腺癌中的预后意义。靶向dnmt3a介导的途径可能为前列腺癌的治疗提供新的治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cancer Genomics & Proteomics
Cancer Genomics & Proteomics ONCOLOGY-GENETICS & HEREDITY
CiteScore
5.00
自引率
8.00%
发文量
51
期刊介绍: Cancer Genomics & Proteomics (CGP) is an international peer-reviewed journal designed to publish rapidly high quality articles and reviews on the application of genomic and proteomic technology to basic, experimental and clinical cancer research. In this site you may find information concerning the editorial board, editorial policy, issue contents, subscriptions, submission of manuscripts and advertising. The first issue of CGP circulated in January 2004. Cancer Genomics & Proteomics is a journal of the International Institute of Anticancer Research. From January 2013 CGP is converted to an online-only open access journal. Cancer Genomics & Proteomics supports (a) the aims and the research projects of the INTERNATIONAL INSTITUTE OF ANTICANCER RESEARCH and (b) the organization of the INTERNATIONAL CONFERENCES OF ANTICANCER RESEARCH.
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