Evaluating the utility of ZNF331 promoter methylation as a prognostic and predictive marker in stage III colon cancer: results from CALGB 89803 (Alliance).

IF 2.9 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-05-08 DOI:10.1080/15592294.2024.2349980
Elizabeth S Nakasone, Tyler J Zemla, Ming Yu, She Yu Lin, Fang-Shu Ou, Kelly Carter, Federico Innocenti, Leonard Saltz, William M Grady, Stacey A Cohen
{"title":"Evaluating the utility of <i>ZNF331</i> promoter methylation as a prognostic and predictive marker in stage III colon cancer: results from CALGB 89803 (Alliance).","authors":"Elizabeth S Nakasone, Tyler J Zemla, Ming Yu, She Yu Lin, Fang-Shu Ou, Kelly Carter, Federico Innocenti, Leonard Saltz, William M Grady, Stacey A Cohen","doi":"10.1080/15592294.2024.2349980","DOIUrl":null,"url":null,"abstract":"<p><p>While epigenomic alterations are common in colorectal cancers (CRC), few epigenomic biomarkers that risk-stratify patients have been identified. We thus sought to determine the potential of <i>ZNF331</i> promoter hypermethylation (m<i>ZNF331</i>) as a prognostic and predictive marker in colon cancer. We examined the association of m<i>ZNF331</i> with clinicopathologic features, relapse, survival, and treatment efficacy in patients with stage III colon cancer treated within a randomized adjuvant chemotherapy trial (CALGB/Alliance89803). Residual tumour tissue was available for genomic DNA extraction and methylation analysis for 385 patients. <i>ZNF331</i> promoter methylation status was determined by bisulphite conversion and fluorescence-based real-time polymerase chain reaction. Kaplan-Meier estimator and Cox proportional hazard models were used to assess the prognostic and predictive role of m<i>ZNF331</i> in this well-annotated dataset, adjusting for clinicopathologic features and standard molecular markers. m<i>ZNF331</i> was observed in 267/385 (69.4%) evaluable cases. Histopathologic features were largely similar between patients with m<i>ZNF331</i> compared to unmethylated <i>ZNF331</i> (unm<i>ZNFF31</i>). There was no significant difference in disease-free or overall survival between patients with m<i>ZNF331</i> versus unm<i>ZNF331</i> colon cancers, even when adjusting for clinicopathologic features and molecular marker status. Similarly, there was no difference in disease-free or overall survival across treatment arms when stratified by <i>ZNF331</i> methylation status. While <i>ZNF331</i> promoter hypermethylation is frequently observed in CRC, our current study of a small subset of patients with stage III colon cancer suggests limited applicability as a prognostic marker. Larger studies may provide more insight and clarity into the applicability of m<i>ZNF331</i> as a prognostic and predictive marker.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2349980"},"PeriodicalIF":2.9000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11085945/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Epigenetics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1080/15592294.2024.2349980","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/5/8 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

While epigenomic alterations are common in colorectal cancers (CRC), few epigenomic biomarkers that risk-stratify patients have been identified. We thus sought to determine the potential of ZNF331 promoter hypermethylation (mZNF331) as a prognostic and predictive marker in colon cancer. We examined the association of mZNF331 with clinicopathologic features, relapse, survival, and treatment efficacy in patients with stage III colon cancer treated within a randomized adjuvant chemotherapy trial (CALGB/Alliance89803). Residual tumour tissue was available for genomic DNA extraction and methylation analysis for 385 patients. ZNF331 promoter methylation status was determined by bisulphite conversion and fluorescence-based real-time polymerase chain reaction. Kaplan-Meier estimator and Cox proportional hazard models were used to assess the prognostic and predictive role of mZNF331 in this well-annotated dataset, adjusting for clinicopathologic features and standard molecular markers. mZNF331 was observed in 267/385 (69.4%) evaluable cases. Histopathologic features were largely similar between patients with mZNF331 compared to unmethylated ZNF331 (unmZNFF31). There was no significant difference in disease-free or overall survival between patients with mZNF331 versus unmZNF331 colon cancers, even when adjusting for clinicopathologic features and molecular marker status. Similarly, there was no difference in disease-free or overall survival across treatment arms when stratified by ZNF331 methylation status. While ZNF331 promoter hypermethylation is frequently observed in CRC, our current study of a small subset of patients with stage III colon cancer suggests limited applicability as a prognostic marker. Larger studies may provide more insight and clarity into the applicability of mZNF331 as a prognostic and predictive marker.

评估 ZNF331 启动子甲基化作为 III 期结肠癌预后和预测标志物的效用:CALGB 89803(联盟)的研究结果。
虽然表观基因组改变在结直肠癌(CRC)中很常见,但能对患者进行风险分层的表观基因组生物标志物却很少被发现。因此,我们试图确定 ZNF331 启动子高甲基化(mZNF331)作为结肠癌预后和预测标志物的潜力。我们研究了在随机辅助化疗试验(CALGB/Alliance89803)中接受治疗的 III 期结肠癌患者的 mZNF331 与临床病理特征、复发、生存和治疗效果的关系。385名患者的残留肿瘤组织可用于基因组DNA提取和甲基化分析。ZNF331启动子甲基化状态是通过亚硫酸氢盐转化和荧光实时聚合酶链反应确定的。采用 Kaplan-Meier 估计器和 Cox 比例危险模型来评估 mZNF331 在这一注释完备的数据集中的预后和预测作用,并对临床病理特征和标准分子标记进行调整。与未甲基化的 ZNF331(unmZNFF31)相比,mZNF331 患者的组织病理学特征基本相似。mZNF331与unmZNF331结肠癌患者的无病存活率或总存活率没有明显差异,即使对临床病理特征和分子标记状态进行调整也是如此。同样,根据 ZNF331 甲基化状态进行分层后,各治疗组的无病生存率或总生存率也没有差异。虽然 ZNF331 启动子高甲基化在 CRC 中经常被观察到,但我们目前对 III 期结肠癌患者中一小部分人的研究表明,ZNF331 作为预后标志物的适用性有限。更大规模的研究可能会让我们对 mZNF331 作为预后和预测标志物的适用性有更深入的了解和更清晰的认识。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Epigenetics
Epigenetics 生物-生化与分子生物学
CiteScore
6.80
自引率
2.70%
发文量
82
审稿时长
3-8 weeks
期刊介绍: Epigenetics publishes peer-reviewed original research and review articles that provide an unprecedented forum where epigenetic mechanisms and their role in diverse biological processes can be revealed, shared, and discussed. Epigenetics research studies heritable changes in gene expression caused by mechanisms others than the modification of the DNA sequence. Epigenetics therefore plays critical roles in a variety of biological systems, diseases, and disciplines. Topics of interest include (but are not limited to): DNA methylation Nucleosome positioning and modification Gene silencing Imprinting Nuclear reprogramming Chromatin remodeling Non-coding RNA Non-histone chromosomal elements Dosage compensation Nuclear organization Epigenetic therapy and diagnostics Nutrition and environmental epigenetics Cancer epigenetics Neuroepigenetics
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信