Abstract
BackgroundNew 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.MethodsMGMT 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.ResultsLow 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.ConclusionsOur 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.
Highlights
New biomarkers are needed for the prognosis of advanced colorectal cancer, which remains incurable by conventional treatments
In this study of tumors from colorectal cancer (CRC) patients, methylated methylguanine DNA methyltransferase (MGMT) promoter was significantly associated with low MGMT expression intensity and poor-differentiation grade but not with overall survival (OS), disease-free survival (DFS), or tumor stage
MGMT expression intensity can be considered as an independent prognostic factor for OS, but the influence of percentage CD133 expression on the prognosis for DFS depends on the tumor stage
Summary
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. Almost all (95%) of these new CRCs are likely to be adenocarcinomas and, despite recent advances in detection and therapy, 25% of these patients will develop metastasis and have a very low 5-year survival rate of around 10% [2,3]. New biomarkers of CRC are needed to permit an earlier diagnosis and to predict the response to treatment. Carcinoembryonic antigen (CEA) is recommended as a biomarker to detect spread of the cancer and to follow up CRC patients. In the diagnosis of early CRC it has major limitations such as low sensitivity and specificity (36% and 87% respectively).
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