title: Prognostic DNA methylation marker in serum of cancer patients.
abstract: Changes in the status of DNA methylation are among the most common molecular alterations in human neoplasia. Recent demonstrations of tumor-derived methylated DNA in the blood stream of cancer patients allow the use of these epigenetic markers for risk assessment in cancer patients. We were interested in evaluating the prognostic value of several methylated genes in the serum of cancer patients. Using MethyLight, a high-throughput DNA methylation assay, we analyzed 215 serum samples from patients with cervical (n = 93) or breast cancer (n = 122) for DNA methylation changes. In cervical cancer, hypermethylation of three genes (MYOD1, CDH1, and CDH13) in pretreatment sera was statistically significantly associated with a poorer disease outcome. Additionally, for the first time we used a so-called gene evaluation set to identify the most important DNA methylation changes in the serum of breast cancer patients from a long list of candidate genes. In the gene evaluation set, we detected five genes (ESR1, APC, HSD17B4, HIC1, and RASSF1A) using our criteria for further analysis. Finally, two of the evaluated genes (APC and RASSF1A) proved to be independent prognostic parameters in breast cancer patients. In summary, we detected several prognostic DNA methylation markers in the serum of cervical and breast cancer patients. This finding indicates great potential for the use of these epigenetic markers in clinical, routine risk assessment in patients with various malignancies.
authors.affiliation: Department of General and Transplant Surgery, Innsbruck Medical University, A-6020 Innsbruck, Austria.
authors.forename: Hannes M
authors.initials: HM
authors.lastname: Müller
authors.forename: Heidi
authors.initials: H
authors.lastname: Fiegl
authors.forename: Andreas
authors.initials: A
authors.lastname: Widschwendter
authors.forename: Martin
authors.initials: M
authors.lastname: Widschwendter
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics / Q000401:mortality; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000097:blood* / Q000235:genetics*; D005260:Female; D017491:Genes, APC; D006801:Humans; D015999:Multivariate Analysis; D011379:Prognosis; D015996:Survival Rate; D025521:Tumor Suppressor Proteins / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000097:blood / Q000235:genetics / Q000401:mortality
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins