ERCC1 and MGMT Methylation as a Predictive Marker of Relapse and FOLFOX Response in Colorectal Cancer Patients from South Tunisia

Author:

Jamai Dhouha12,Gargouri Raja3,Selmi Boulbaba1,Khabir Abdelmajid2

Affiliation:

1. Research Laboratory of Bioresources, Integrative Biology and Valorization LR14ES06, Higher Institute of Biotechnology of Monastir, University of Monastir, Avenue Tahar Haaadded, BP 74, Monastir 5000, Tunisia

2. Department of Pathology, Habib Bourguiba University Hospital, Medenine 4100, Tunisia

3. Laboratory of Molecular Biotechnology of Eukaryotes, Biotechnology Center, University of Sfax, Avenue Sidi Mansour, Sfax 3018, Tunisia

Abstract

Genetic and epigenetic modifications present a major cause of relapse and treatment failure in colorectal cancer. This study aims to appreciate the prognostic and predictive value of ERRC1 and MGMT methylation. We also studied the prognostic impact of the ERCC1 rs11615 polymorphism as well as its expression. Methylation profiles of ERCC1 and MGMT were tested by methylation-specific PCR. A polymorphism of ERCC1 was studied using PCR-RFLP and its expression was examined by immunohistochemistry. ERCC1 was methylated in 44.6% of colorectal adenocarcinoma while MGMT was methylated in 69% of cases. MGMT methylation was strongly associated with lymph node metastasis, lymph invasion, venous invasion, perineural invasion, distant metastasis and relapse. Patients with methylation of both genes were more likely to have a poor prognosis and display chemoresistance. IHC analysis revealed that ERCC1 staining was noted in 52.8% of colorectal adenocarcinoma and inversely related to distant metastasis and cancer recurrence. Kaplan Meier analysis revealed that the worst overall survival was significantly associated with ERCC1 and MGMT methylation while decreased ERCC1 expression and T/T genotype exhibited the best overall survival. The methylation of MGMT, alone or combined with ERCC1, is predictive for poor prognosis, short overall survival and chemotherapy response in colorectal cancer.

Funder

Ministry of Higher Education and Scientific Research, Tunisia

University of Monastir and University Department of Pathology

Habib Bourguiba University Hospital of Medenine, Tunisia

Publisher

MDPI AG

Subject

Genetics (clinical),Genetics

Reference33 articles.

1. DNA Repair Mechanisms in Cancer Development and Therapy;Torgovnick;Front. Genet.,2015

2. Platinum Resistance: The Role of DNA Repair Pathways;Martin;Clin. Cancer Res.,2008

3. Role of MGMT in Tumor Development, Progression, Diagnosis, Treatment and Prognosis;Sharma;Anticancer Res.,2009

4. Eukaryotic Nucleotide Excision Repair: From Understanding Mechanisms to Influencing Biology;Shuck;Cell Res.,2008

5. DNA Excision Repair;Sancar;Annu. Rev. Biochem.,1996

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3