title: Prognostic significance of methylated RASSF1A and PITX2 genes in blood- and bone marrow plasma of breast cancer patients.
abstract: Free circulating DNA is increased in the serum/plasma of cancer patients, and methylation of certain genes has been found to be characteristic for malignancy. Therefore, we investigated the prognostic value of two promising genes, PITX2 and RASSF1A, in peripheral blood-plasma (PB-P) and bone marrow plasma (BM-P) of breast cancer patients. Peripheral blood and bone marrow samples from patients with primary breast cancer were prospectively collected during primary surgery at the Department of Obstetrics and Gynecology in Innsbruck (n = 428) from June 2000 to December 2006. The study has been approved by the ethical committee of the Medical University of Innsbruck. Methylation analysis was performed using MethyLight, a methylation-specific quantitative PCR-method. In univariate survival analysis, methylated PITX2 in PB-P was found to be a significant indicator for poor overall survival (OAS) and distant disease-free survival (DDFS) (P = 0.001 and P = 0.023). Methylated RASSF1A in PB-P was also an indicator for poor OAS and DDFS (P = 0.001 and P = 0.004). RASSF1A had also significant prognostic potential when determined in BM-P (P = 0.016). In multivariate survival analysis methylated PITX2 and RASSF1A in PB-P remained as therapy-independent prognostic factors for OAS (P = 0.021, P < 0.001). For DDFS only RASSF1A in PB-P showed prognostic significance (P = 0.002). Methylated RASSF1A and PITX2 in PB-P appear to have promising potential as prognostic markers in clinical use.
authors.affiliation: Department of Medical Statistics, Informatics and Health Economics, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Göbel
authors.forename: Doris
authors.initials: D
authors.lastname: Auer
authors.forename: Inge
authors.initials: I
authors.lastname: Gaugg
authors.forename: Alois
authors.initials: A
authors.lastname: Schneitter
authors.forename: Ralf
authors.initials: R
authors.lastname: Lesche
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Müller-Holzner
authors.forename: Christian
authors.initials: C
authors.lastname: Marth
authors.forename: Günter
authors.initials: G
authors.lastname: Daxenbichler
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D001853:Bone Marrow / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000097:blood*; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000378:metabolism; D011379:Prognosis; D014157:Transcription Factors / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D000097577:Homeobox Protein PITX2
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D018398:Homeodomain Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000097577:Homeobox Protein PITX2; C411762:RASSF1 protein, human