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Clinical and prognosis value of the CIMP status combined with MLH1 or p16 INK4a methylation in colorectal cancer

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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.

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Acknowledgements

The authors thank Professor A. Gargouri for helpful discussion. This work was supported by a grant from the Tunisian Ministry of Higher Education and Scientific Research.

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Authors and Affiliations

  1. Laboratory of Molecular Biotechnology of Eukaryotes, Department of Cancer Genetics, Center of Biotechnology of Sfax, University of Sfax, BPK1177, 3018, Sfax, Tunisia

    Amana Saadallah-Kallel, Rania Abdelmaksoud-Dammak, Mouna Triki & Raja Mokdad-Gargouri

  2. Service of Pathology, Habib Bourguiba Hospital, Sfax, Tunisia

    Slim Charfi, Abdelmajid Khabir & Tahia Sallemi-Boudawara

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  1. Amana Saadallah-Kallel
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  2. Rania Abdelmaksoud-Dammak
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Correspondence to Raja Mokdad-Gargouri.

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The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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Ethical approval was given by the Ethics Committee of Habib Bourguiba Hospital–Sfax-Tunisia.

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Informed consent was obtained from all individual participants included in the study, giving their authorization to access their clinical information and tumor samples for research purpose.

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Saadallah-Kallel, A., Abdelmaksoud-Dammak, R., Triki, M. et al. Clinical and prognosis value of the CIMP status combined with MLH1 or p16 INK4a methylation in colorectal cancer. Med Oncol 34, 147 (2017). https://doi.org/10.1007/s12032-017-1007-1

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