Clinical and prognosis value of the CIMP status combined with MLH1 or p16 INK4a methylation in colorectal cancer
| Autor: | Amana Saadallah-Kallel, Raja Mokdad-Gargouri, Slim Charfi, Abdelmajid Khabir, Rania Abdelmaksoud-Dammak, Tahia Sallemi-Boudawara, Mouna Triki |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cancer Research medicine.medical_specialty Lymphovascular invasion Colorectal cancer MLH1 03 medical and health sciences 0302 clinical medicine Internal medicine Medicine Stage (cooking) neoplasms Hematology CpG Island Methylator Phenotype business.industry nutritional and metabolic diseases General Medicine Methylation medicine.disease digestive system diseases 030104 developmental biology Oncology CpG site 030220 oncology & carcinogenesis Cancer research business |
| Zdroj: | Medical Oncology. 34 |
| ISSN: | 1559-131X 1357-0560 |
| Popis: | Aberrant DNA methylation of CpG islands occurred frequently in CRC and associated with transcriptional silencing of key genes. In this study, the CIMP combined with MLH1 or p16 INK4a methylation status was determined in CRC patients and correlated with clinicopathological parameters and overall survival. Our data showed that CIMP+ CRCs were identified in 32.9% of cases and that CACNAG1 is the most frequently methylated promoter. When we combined the CIMP with the MLH1 or the p16 INK4a methylation status, we found that CIMP−/MLH1-U (37.8%) and CIMP−/p16 INK4a -U (35.4%) tumors were the most frequent among the four subtypes. Statistical analysis showed that tumor location, lymphovascular invasion, TNM stage, and MSI differed among the group of patients. Kaplan–Meier analyses revealed differences in overall survival according to the CIMP combined with MLH1 or p16 INK4a methylation status. In a multivariate analysis, CIMP/MLH1 and CIMP/p16 INK4a methylation statuses were predictive of prognosis, and the OS was longer for patients with tumors CIMP−/MLH1-M, as well as CIMP−/p16 INK4a -M. Furthermore, DNMT1 is significantly overexpressed in tumors than in normal tissues as well as in CIMP+ than CIMP− tumors. Our results suggest that tumor classification based on the CIMP status combined with MLH1 or p16 INK4a methylation is useful to predict prognosis in CRC patients. |
| Databáze: | OpenAIRE |
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