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Please use this identifier to cite or link to this item: http://hdl.handle.net/10481/33448

Title: Hypermethylated 14-3-3-σ and ESR1 gene promoters in serum as candidate biomarkers for the diagnosis and treatment efficacy of breast cancer metastasis
Authors: Zurita, Mercedes
Lara Jiménez, Pedro Carlos
Moral Ávila, Rosario del
Torres, Blanca
Linares-Fernández, José Luis
Ríos-Arrabal, Sandra
Martínez-Galán, Joaquina
Oliver, Francisco Javier
Ruiz de Almodóvar, Mariano
Issue Date: 2010
Abstract: Background: Numerous hypermethylated genes have been reported in breast cancer, and the silencing of these genes plays an important role in carcinogenesis, tumor progression and diagnosis. These hypermethylated promoters are very rarely found in normal breast. It has been suggested that aberrant hypermethylation may be useful as a biomarker, with implications for breast cancer etiology, diagnosis, and management. The relationship between primary neoplasm and metastasis remains largely unknown. There has been no comprehensive comparative study on the clinical usefulness of tumor-associated methylated DNA biomarkers in primary breast carcinoma and metastatic breast carcinoma. The objective of the present study was to investigate the association between clinical extension of breast cancer and methylation status of Estrogen Receptor1 (ESR1) and Stratifin (14-3-3-σ) gene promoters in disease-free and metastatic breast cancer patients. Methods: We studied two cohorts of patients: 77 patients treated for breast cancer with no signs of disease, and 34 patients with metastatic breast cancer. DNA was obtained from serum samples, and promoter methylation status was determined by using DNA bisulfite modification and quantitative methylation-specific PCR. Results: Serum levels of methylated gene promoter 14-3-3-σ significantly differed between Control and Metastatic Breast Cancer groups (P < 0.001), and between Disease-Free and Metastatic Breast Cancer groups (P < 0.001). The ratio of the 14-3-3-σ level before the first chemotherapy cycle to the level just before administration of the second chemotherapy cycle was defined as the Biomarker Response Ratio [BRR]. We calculated BRR values for the "continuous decline" and "rise-and-fall" groups. Subsequent ROC analysis showed a sensitivity of 75% (95% CI: 47.6 - 86.7) and a specificity of 66.7% (95% CI: 41.0 - 86.7) to discriminate between the groups for a cut-off level of BRR = 2.39. The area under the ROC curve (Z = 0.804 ± 0.074) indicates that this test is a good approach to post-treatment prognosis. Conclusions: The relationship of 14-3-3-σ with breast cancer metastasis and progression found in this study suggests a possible application of 14-3-3-σ as a biomarker to screen for metastasis and to follow up patients treated for metastatic breast cancer, monitoring their disease status and treatment response.
Sponsorship: This study was supported by a grant from the Ministerio de Ciencia e Innovación: SAF 2004-00889; JL Linares is supported by the Junta de Andalucía (P06-CTS-1385).
Publisher: Biomed Central
Keywords: Breast cancer
Cancer metastasis
Treatment
Estrogen Receptor1 (ER1)
Biomarkers
URI: http://hdl.handle.net/10481/33448
ISSN: 1471-2407
Rights : Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License
Citation: Zurita, M.; et al. Hypermethylated 14-3-3-σ and ESR1 gene promoters in serum as candidate biomarkers for the diagnosis and treatment efficacy of breast cancer metastasis. BMC Cancer, 10: 217 (2010). [http://hdl.handle.net/10481/33448]
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