The Clinical Significance of Promoter Methylation of Fluoropyrimidine Metabolizing and Cyclooxygenase Genes in Colorectal Cancer.

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC
ACS Applied Electronic Materials Pub Date : 2021-02-14 eCollection Date: 2021-01-01 DOI:10.1177/2516865720986231
Mariam Ahmed Fouad, Salem Eid Salem, Marwa M Hussien, Doaa Mohamed Badr, Abdelrahman N Zekri, Hafez Farouk Hafez, Samia A Shouman
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引用次数: 2

Abstract

Aims: This study investigated the impact of promoter methylation of flouropyrimidine (FP) metabolizing and cyclooxygenase 2 (COX2) genes on their mRNA expression and on the clinical outcome of colorectal cancer (CRC) patients.

Methods: Methylation specific-PCR and real time-PCR of thymidylate synthase (TS), thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD) and COX2 were performed at baseline and after 3 and 6 months of FP therapy. Pairwise comparisons were conducted between the subgroups of CRC patients. The event free survival (EFS) and the hazard of progression were estimated by univariate and multivariate analyses.

Results: At baseline CRC patients, both TS and TP were overexpressed, in spite of the unmethylation of TS and the full methylation of TP genes. Significant downexpression of DPD and COX2 were associated their promoter's methylation. At the end of FP therapy, TS, DPD and COX2 were overexpressed by 7.52, 2.88 and 3.45 folds, respectively, while TP was downexpressed by 0.54 fold. However, no change was observed in the methylation status of genes with FP therapy. Pairwise comparisons revealed significant difference in the expression and the methylation status of genes according to the clinicopathological characters of CRC patients either at baseline or after FP therapy. The overexpression of DPD and COX2 genes were indicators for a poor EFS of CRC patients. Also, the high level of COX2 expression was found to be significantly correlated with the hazard of progression (HR = 1.73, 95% CI = 1.02-3.03).

Conclusion: The promoter methylation of FP metabolizing and COX2 genes has significant impact on the expression and the treatment outcome of CRC patients.

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结直肠癌氟嘧啶代谢和环加氧酶基因启动子甲基化的临床意义。
目的:研究氟嘧啶(FP)代谢和环氧化酶2 (COX2)基因启动子甲基化对结直肠癌(CRC)患者mRNA表达及临床预后的影响。方法:在基线和FP治疗3、6个月后分别对胸腺嘧啶合成酶(TS)、胸腺嘧啶磷酸化酶(TP)、二氢嘧啶脱氢酶(DPD)和COX2进行甲基化特异性pcr和实时pcr检测。在结直肠癌患者亚组之间进行两两比较。通过单因素和多因素分析估计无事件生存期(EFS)和进展危险。结果:在基线CRC患者中,尽管TS基因未甲基化,TP基因完全甲基化,但TS和TP基因均过表达。DPD和COX2的显著下调与其启动子甲基化相关。FP治疗结束时,TS、DPD和COX2分别高表达7.52倍、2.88倍和3.45倍,TP低表达0.54倍。然而,在FP治疗中没有观察到基因甲基化状态的变化。两两比较显示,根据CRC患者的临床病理特征,在基线和FP治疗后,基因的表达和甲基化状态有显著差异。DPD和COX2基因的过表达是结直肠癌患者EFS较差的指标。此外,高水平的COX2表达与进展风险显著相关(HR = 1.73, 95% CI = 1.02-3.03)。结论:FP代谢和COX2基因启动子甲基化对结直肠癌患者的表达和治疗结果有显著影响。
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
CiteScore
7.20
自引率
4.30%
发文量
567
期刊介绍: ACS Applied Electronic Materials is an interdisciplinary journal publishing original research covering all aspects of electronic materials. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrate knowledge in the areas of materials science, engineering, optics, physics, and chemistry into important applications of electronic materials. Sample research topics that span the journal's scope are inorganic, organic, ionic and polymeric materials with properties that include conducting, semiconducting, superconducting, insulating, dielectric, magnetic, optoelectronic, piezoelectric, ferroelectric and thermoelectric. Indexed/​Abstracted: Web of Science SCIE Scopus CAS INSPEC Portico
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