Published in:
01-08-2017 | Original Paper
Clinical and prognosis value of the CIMP status combined with MLH1 or p16
INK4a
methylation in colorectal cancer
Authors:
Amana Saadallah-Kallel, Rania Abdelmaksoud-Dammak, Mouna Triki, Slim Charfi, Abdelmajid Khabir, Tahia Sallemi-Boudawara, Raja Mokdad-Gargouri
Published in:
Medical Oncology
|
Issue 8/2017
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Abstract
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.