Τίτλος:
CST6 promoter methylation in circulating cell-free DNA of breast cancer patients
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Objectives: We have recently shown that detection of CST6 promoter methylation in primary breast tumors can provide important prognostic information in patients with operable breast cancer and that CST6 promoter is also methylated in Circulating Tumor Cells (CTC). In this study we evaluated the presence of CST6 promoter methylation in cell-free DNA (cfDNA) circulating in plasma of breast cancer patients. Design and methods: Our study material consisted of: a) a pilot testing group of 27 patients with stage I-III operable breast cancer, 46 patients with verified metastasis and 37 healthy donors and b) an independent cohort of 123 consecutive stage I-III operable breast cancer patients. Methylated and unmethylated CST6 promoter sequences were detected by using methylation-specific PCR (MSP). CST6 immunohistochemical detection was performed in 20 corresponding primary tumor tissues. Results: In the pilot testing group, CST6 promoter was methylated in 8/27 (29.6%) operable breast cancer patients, in 6/46 (13.0%) patients with verified metastasis but none of 37 healthy individuals (0%). In the independent cohort, 49/123 (39.8%) operable breast cancer patients were found positive. During the follow up period, 25/123 (20.3%) patients relapsed and 9/123 (7.3%) died. CST6 was methylated in cfDNA of 13/25 (52%) patients that relapsed and in 3/9 (33.3%) patients that died. Conclusions: CST6 promoter is highly methylated in cfDNA of breast cancer patients, but not in healthy individuals. CST6 promoter methylation in cfDNA, should be prospectively validated as a novel plasma tumor biomarker for breast cancer in a large cohort of breast cancer patients. © 2012 The Canadian Society of Clinical Chemists.
Συγγραφείς:
Chimonidou, M.
Tzitzira, A.
Strati, A.
Sotiropoulou, G.
Sfikas, C.
Malamos, N.
Georgoulias, V.
Lianidou, E.
Περιοδικό:
Clinical Biochemistry
Λέξεις-κλειδιά:
antineoplastic agent; cell free DNA; cystatin M; DNA; unclassified drug, adult; article; breast cancer; cancer prognosis; cancer surgery; circulating tumor cell; controlled study; CST6 gene; DNA methylation; DNA sequence; female; gene expression; human; human cell; human tissue; immunohistochemistry; major clinical study; metastasis; polymerase chain reaction; priority journal; promoter region; sensitivity and specificity, Breast Neoplasms; Case-Control Studies; Cystatin M; DNA Methylation; DNA, Neoplasm; Female; Follow-Up Studies; Humans; Immunohistochemistry; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplastic Cells, Circulating; Pilot Projects; Predictive Value of Tests; Prognosis; Promoter Regions, Genetic; Sensitivity and Specificity; Tumor Markers, Biological
DOI:
10.1016/j.clinbiochem.2012.09.015
