دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: The Clinical Significance of Promoter Methylation of Fluoropyrimidine Metabolizing and Cyclooxygenase Genes in Colorectal Cancer.
المؤلفون: Fouad MA; Pharmacology and Experimental Oncology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Egypt., Salem SE; Medical Oncology Department, National Cancer Institute, Cairo University, Egypt., Hussien MM; Medical Oncology Department, National Cancer Institute, Cairo University, Egypt., Badr DM; Pharmacology and Experimental Oncology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Egypt., Zekri AN; Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Egypt., Hafez HF; Pharmacology and Experimental Oncology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Egypt., Shouman SA; Pharmacology and Experimental Oncology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Egypt.
المصدر: Epigenetics insights [Epigenet Insights] 2021 Feb 14; Vol. 14, pp. 2516865720986231. Date of Electronic Publication: 2021 Feb 14 (Print Publication: 2021).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: SAGE Publications Country of Publication: United States NLM ID: 101735398 Publication Model: eCollection Cited Medium: Internet ISSN: 2516-8657 (Electronic) Linking ISSN: 25168657 NLM ISO Abbreviation: Epigenet Insights Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [Thousand Oaks, CA] : SAGE Publications, [2018]-[2023]
مستخلص: 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.
Competing Interests: Declaration of Conflicting Interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.
(© The Author(s) 2021.)
References: Anticancer Res. 2013 Aug;33(8):3137-43. (PMID: 23898071)
PLoS One. 2012;7(3):e31808. (PMID: 22412841)
Exp Oncol. 2014 Dec;36(4):267-70. (PMID: 25537222)
BMC Gastroenterol. 2014 Jan 02;14:1. (PMID: 24383454)
Cancer Res. 1992 Sep 15;52(18):4922-8. (PMID: 1516048)
PLoS One. 2014 Mar 20;9(3):e92599. (PMID: 24651295)
PLoS One. 2014 Mar 27;9(3):e92305. (PMID: 24676085)
BMC Cancer. 2010 Sep 01;10:470. (PMID: 20809970)
Int J Clin Exp Pathol. 2015 Oct 01;8(10):12333-45. (PMID: 26722420)
BMC Cancer. 2010 Jul 12;10:366. (PMID: 20618997)
Mol Clin Oncol. 2017 Dec;7(6):943-952. (PMID: 29285354)
BMC Cancer. 2015 Dec 16;15:979. (PMID: 26674784)
Genes (Basel). 2017 May 23;8(6):. (PMID: 28545252)
World J Gastroenterol. 2014 May 28;20(20):6055-72. (PMID: 24876728)
Clin Colorectal Cancer. 2002 Feb;1(4):220-9. (PMID: 12450420)
Clin Cancer Res. 2005 Dec 15;11(24 Pt 1):8699-705. (PMID: 16361556)
Br J Cancer. 2012 Dec 4;107(12):1950-5. (PMID: 23169295)
Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9821-6. (PMID: 8790415)
Br J Cancer. 2005 Jan 31;92(2):259-64. (PMID: 15655543)
Cancer Prev Res (Phila). 2011 Nov;4(11):1728-35. (PMID: 21778329)
Front Pharmacol. 2018 Oct 18;9:1173. (PMID: 30405408)
Int J Mol Sci. 2015 Jan 22;16(2):2472-96. (PMID: 25622259)
Ther Adv Med Oncol. 2016 Jan;8(1):57-84. (PMID: 26753006)
Biochim Biophys Acta. 2002 Jul 18;1587(2-3):174-82. (PMID: 12084459)
Curr Enzym Inhib. 2012 Sep 1;8(2):118-123. (PMID: 24683387)
Cancers (Basel). 2013 Jun 05;5(2):676-713. (PMID: 24216997)
BMC Cancer. 2011 Jun 13;11:238. (PMID: 21668942)
Signal Transduct Target Ther. 2020 Mar 20;5(1):22. (PMID: 32296018)
Eur J Pharmacol. 2009 Oct 1;619(1-3):8-14. (PMID: 19695243)
BMC Clin Pathol. 2014 Jun 10;14:25. (PMID: 24936150)
Cancer Microenviron. 2016 Apr;9(1):33-43. (PMID: 26298314)
Oncol Rep. 2016 Jan;35(1):298-306. (PMID: 26497773)
Front Pharmacol. 2016 Jun 23;7:172. (PMID: 27445811)
Biochem Biophys Res Commun. 2010 Jan 15;391(3):1465-70. (PMID: 20035722)
J Exp Clin Cancer Res. 2008 Oct 20;27:54. (PMID: 18937829)
Pharmacogenet Genomics. 2006 Nov;16(11):809-16. (PMID: 17047489)
Nat Commun. 2017 Mar 17;8:14617. (PMID: 28303888)
Clin Cancer Res. 2006 Jun 15;12(12):3864; author reply 3864. (PMID: 16778115)
Cancer Chemother Pharmacol. 2008 Apr;61(5):775-84. (PMID: 17624531)
Br J Cancer. 2010 Sep 7;103(6):870-6. (PMID: 20717110)
Cancer Cell. 2014 Oct 13;26(4):577-90. (PMID: 25263941)
Methods Mol Biol. 2007;373:89-102. (PMID: 17185760)
Oncogene. 2017 Aug;36(31):4415-4426. (PMID: 28346420)
Br J Cancer. 2014 May 27;110(11):2728-37. (PMID: 24800948)
Fam Cancer. 2016 Jul;15(3):405-12. (PMID: 26875156)
Nucleic Acids Res. 2003 May 1;31(9):e50. (PMID: 12711695)
Expert Opin Drug Metab Toxicol. 2017 Apr;13(4):387-398. (PMID: 27860490)
Anticancer Res. 2012 May;32(5):1757-62. (PMID: 22593457)
فهرسة مساهمة: Keywords: Colorectal cancer; cyclooxygenase 2; fluoropyrimidine metabolizing; gene expression; promoter methylation; survival and progression
تواريخ الأحداث: Date Created: 20210301 Latest Revision: 20231110
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC7890744
DOI: 10.1177/2516865720986231
PMID: 33644686
قاعدة البيانات: MEDLINE
الوصف
تدمد:2516-8657
DOI:10.1177/2516865720986231