| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Imaging, Diagnosis, Prognosis |
Authors' Affiliations: Departments of 1 Medicine II, 2 Medical Informatics, Biometry, and Epidemiology, and 3 Institute of Clinical Chemistry, University Hospital Grosshadern, University of Munich, Munich, Germany
Requests for reprints: Frank T. Kolligs, Department of Medicine II, University Hospital Grosshadern, Marchioninistrasse 15, 81377 Munich, Germany. Phone: 49-89-7095-3130; Fax: 49-89-7095-6183; E-mail: fkolligs{at}med.uni-muenchen.de.
Purpose: Aberrant CpG island hypermethylation is a feature of a subgroup of colorectal cancers, which can be detected in the serum of affected patients. This study was designed to identify methylation targets with prognostic significance in the serum of patients with colorectal cancer.
Experimental Design: In a gene evaluation set consisting of sera from 24 patients with local colorectal cancers, 14 with metastasized disease, and 20 healthy controls, the genes HPP1/TPEF, HLTF, and hMLH1 were identified as potential serum DNA methylation markers. These genes were further analyzed in a test set of sera of 104 patients with colorectal cancer.
Results: Methylation of HLTF, HPP1/TPEF, and hMLH1 was found to be significantly correlated with tumor size, and methylation of HLTF and HPP1/TPEF was significantly associated with metastatic disease and tumor stage. Moreover, methylation of HPP1/TPEF was also associated with serum carcinoembryonic antigen. The prognostic relevance of methylation of these genes was tested in pretherapeutic sera of 77 patients with known follow-up. Patients with methylation of HPP1/TPEF or HLTF were found to have unfavorable prognosis (P = 0.001 and 0.008). In contrast, serum methylation of hMLH1 was not associated with a higher risk of death. Multivariate analysis showed methylated HPP1 and/or HLTF serum DNA to be independently associated with poor outcome and a relative risk of death of 3.4 (95% confidence interval, 1.4-8.1; P = 0.007).
Conclusions: These data show that the methylation status of specific genes in the serum of patients with colorectal cancer has the potential to become a pretherapeutic predictor of outcome.
Related Article
Clin. Cancer Res. 2006 12: 7205-7208.
This article has been cited by other articles:
|
|
 |
|
  S. Yagyu, T. Gotoh, T. Iehara, M. Miyachi, Y. Katsumi, S. Tsubai-Shimizu, K. Kikuchi, S. Tamura, K. Tsuchiya, T. Imamura, et al. Circulating Methylated-DCR2 Gene in Serum as an Indicator of Prognosis and Therapeutic Efficacy in Patients with MYCN Nonamplified Neuroblastoma Clin. Cancer Res., November 1, 2008; 14(21): 7011 - 7019. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. F. Ransohoff, C. Martin, W. S. Wiggins, B. A. Hitt, T. O. Keku, J. A. Galanko, and R. S. Sandler Assessment of Serum Proteomics to Detect Large Colon Adenomas Cancer Epidemiol. Biomarkers Prev., August 1, 2008; 17(8): 2188 - 2193. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Holdenrieder, F. T. Kolligs, and P. Stieber New Horizons for Diagnostic Applications of Circulating Nucleosomes in Blood? Clin. Chem., July 1, 2008; 54(7): 1104 - 1106. [Full Text] [PDF]
|
|
|
|
|
|
C. Lofton-Day, F. Model, T. DeVos, R. Tetzner, J. Distler, M. Schuster, X. Song, R. Lesche, V. Liebenberg, M. Ebert, et al. DNA Methylation Biomarkers for Blood-Based Colorectal Cancer Screening Clin. Chem., February 1, 2008; 54(2): 414 - 423. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Widschwendter and U. Menon Circulating Methylated DNA: A New Generation of Tumor Markers Clin. Cancer Res., December 15, 2006; 12(24): 7205 - 7208. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
