title: Prognostic impact of MGMT promoter methylation and MGMT and CD133 expression in colorectal adenocarcinoma.
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.
authors.forename: Jaime Antonio
authors.initials: JA
authors.lastname: Oliver
authors.forename: Raúl
authors.initials: R
authors.lastname: Ortiz
authors.affiliation: Institute of Biopathology and Regenerative Medicine (IBIMER), University of Granada, Granada 18100, Spain. melguizo@ugr.es.
authors.forename: Consolación
authors.initials: C
authors.lastname: Melguizo
authors.forename: Pablo Juan
authors.initials: PJ
authors.lastname: Alvarez
authors.forename: Jaime
authors.initials: J
authors.lastname: Gómez-Millán
authors.forename: Jose
authors.initials: J
authors.lastname: Prados
mesh_terms: D000071916:AC133 Antigen; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D003430:Cross-Sectional Studies; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics* / Q000378:metabolism*; D045643:DNA Repair Enzymes / Q000235:genetics* / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes