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Open Access Highly Accessed Research article

Prognostic impact of MGMT promoter methylation and MGMT and CD133 expression in colorectal adenocarcinoma

Jaime Antonio Oliver1, Raúl Ortiz123, Consolación Melguizo134*, Pablo Juan Álvarez13, Jaime Gómez-Millán5 and Jose Prados134

Author Affiliations

1 Institute of Biopathology and Regenerative Medicine (IBIMER), University of Granada, Granada 18100, Spain

2 Department of Health Sciences, University of Jaén, Jaén 23071, Spain

3 Biosanitary Institute of Granada (ibs.GRANADA), SAS-Universidad de Granada, Granada, Spain

4 Department of Anatomy and Embryology, University of Granada, Granada 18012, Spain

5 Radiation Oncology Department, Hospital Clinico Universitario Virgen de la Victoria, Málaga 29010, Spain

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BMC Cancer 2014, 14:511  doi:10.1186/1471-2407-14-511

Published: 11 July 2014

Abstract

Background

New biomarkers are needed for the prognosis of advanced colorectal cancer, which remains incurable by conventional treatments. O6-methylguanine DNA methyltransferase (MGMT) methylation and protein expression have been related to colorectal cancer treatment failure and tumor progression. Moreover, the presence in these tumors of cancer stem cells, which are characterized by CD133 expression, has been associated with chemoresistance, radioresistance, metastasis, and local recurrence. The objective of this study was to determine the prognostic value of CD133 and MGMT and their possible interaction in colorectal cancer patients.

Methods

MGMT and CD133 expression was analyzed by immunohistochemistry in 123 paraffin-embedded colorectal adenocarcinoma samples, obtaining the percentage staining and intensity. MGMT promoter methylation status was obtained by using bisulfite modification and methylation-specific PCR (MSP). These values were correlated with clinical data, including overall survival (OS), disease-free survival (DFS), tumor stage, and differentiation grade.

Results

Low MGMT expression intensity was significantly correlated with shorter OS and was a prognostic factor independently of treatment and histopathological variables. High percentage of CD133 expression was significantly correlated with shorter DFS but was not an independent factor. Patients with low-intensity MGMT expression and ≥50% CD133 expression had the poorest DFS and OS outcomes.

Conclusions

Our results support the hypothesis that MGMT expression may be an OS biomarker as useful as tumor stage or differentiation grade and that CD133 expression may be a predictive biomarker of DFS. Thus, MGMT and CD133 may both be useful for determining the prognosis of colorectal cancer patients and to identify those requiring more aggressive adjuvant therapies. Future studies will be necessary to determine its clinical utility.

Keywords:
Colorectal cancer; MGMT; CD133; Methylation status; Biomarker; Overall survival; Disease free-survival