ERCC1 and MGMT Methylation as a Predictive Marker of Relapse and FOLFOX Response in Colorectal Cancer Patients from South Tunisia
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 ex...
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MDPI AG
2023-07-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/14/7/1467 |
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| author | Dhouha Jamai Raja Gargouri Boulbaba Selmi Abdelmajid Khabir |
| author_facet | Dhouha Jamai Raja Gargouri Boulbaba Selmi Abdelmajid Khabir |
| author_sort | Dhouha Jamai |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T01:03:06Z |
| format | Article |
| id | doaj.art-c8c868ed6f864cf693f110ce9e7c8887 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-11T01:03:06Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-c8c868ed6f864cf693f110ce9e7c88872023-11-18T19:30:54ZengMDPI AGGenes2073-44252023-07-01147146710.3390/genes14071467ERCC1 and MGMT Methylation as a Predictive Marker of Relapse and FOLFOX Response in Colorectal Cancer Patients from South TunisiaDhouha Jamai0Raja Gargouri1Boulbaba Selmi2Abdelmajid Khabir3Research Laboratory of Bioresources, Integrative Biology and Valorization LR14ES06, Higher Institute of Biotechnology of Monastir, University of Monastir, Avenue Tahar Haaadded, BP 74, Monastir 5000, TunisiaLaboratory of Molecular Biotechnology of Eukaryotes, Biotechnology Center, University of Sfax, Avenue Sidi Mansour, Sfax 3018, TunisiaResearch Laboratory of Bioresources, Integrative Biology and Valorization LR14ES06, Higher Institute of Biotechnology of Monastir, University of Monastir, Avenue Tahar Haaadded, BP 74, Monastir 5000, TunisiaDepartment of Pathology, Habib Bourguiba University Hospital, Medenine 4100, TunisiaGenetic 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.https://www.mdpi.com/2073-4425/14/7/1467colorectal cancerMGMTERCC1methylationrelapseFOLFOX response |
| spellingShingle | Dhouha Jamai Raja Gargouri Boulbaba Selmi Abdelmajid Khabir ERCC1 and MGMT Methylation as a Predictive Marker of Relapse and FOLFOX Response in Colorectal Cancer Patients from South Tunisia Genes colorectal cancer MGMT ERCC1 methylation relapse FOLFOX response |
| title | ERCC1 and MGMT Methylation as a Predictive Marker of Relapse and FOLFOX Response in Colorectal Cancer Patients from South Tunisia |
| title_full | ERCC1 and MGMT Methylation as a Predictive Marker of Relapse and FOLFOX Response in Colorectal Cancer Patients from South Tunisia |
| title_fullStr | ERCC1 and MGMT Methylation as a Predictive Marker of Relapse and FOLFOX Response in Colorectal Cancer Patients from South Tunisia |
| title_full_unstemmed | ERCC1 and MGMT Methylation as a Predictive Marker of Relapse and FOLFOX Response in Colorectal Cancer Patients from South Tunisia |
| title_short | ERCC1 and MGMT Methylation as a Predictive Marker of Relapse and FOLFOX Response in Colorectal Cancer Patients from South Tunisia |
| title_sort | ercc1 and mgmt methylation as a predictive marker of relapse and folfox response in colorectal cancer patients from south tunisia |
| topic | colorectal cancer MGMT ERCC1 methylation relapse FOLFOX response |
| url | https://www.mdpi.com/2073-4425/14/7/1467 |
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