RT Journal Article
T1 Hypermethylated 14-3-3-sigma and ESR1 gene promoters in serum as candidate biomarkers for the diagnosis and treatment efficacy of breast cancer metastasis
A1 Zurita, Mercedes
A1 Lara, Pedro C
A1 Moral, Rosario del
A1 Torres, Blanca
A1 Linares-Fernández, José Luis
A1 Ríos Arrabal, Sandra
A1 Martínez-Galán, Joaquina
A1 Oliver, Francisco Javier
A1 Ruiz de Almodóvar, José Mariano
K1 Proteinas 14-3-3
K1 Neoplasias de la Mama
K1 Carcinoma
K1 Quimioterapia
K1 Estudios de Cohortes
K1 Metilación de ADN
K1 ADN de Neoplasias
K1 Supervivencia sin Enfermedad
K1 Receptor alfa de Estrógeno
K1 Exonucleasas
K1 Femenino
K1 Humanos
K1 Proteínas de Neoplasias
K1 Estadificación de Neoplasias
K1 Reacción en Cadena de la Polimerasa
K1 Valor Predictivo de las Pruebas
K1 Regiones Promotoras Genéticas
K1 España
K1 Factores de Tiempo
K1 Resultado del Tratamiento
AB 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 abiomarker, with implications for breast cancer etiology, diagnosis, and management. The relationship between primaryneoplasm 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 andmetastatic 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 ratioof 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 areaunder 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.
PB BioMed Central
YR 2010
FD 2010-05-20
LK http://hdl.handle.net/10668/420
UL http://hdl.handle.net/10668/420
LA en
NO Zurita M, Lara PC, Moral R del, Torres B, Linares-Fernández JL, Ríos Arrabal S, et al. Hypermethylated 14-3-3-sigma and ESR1 gene promoters in serum as candidate biomarkers for the diagnosis and treatment efficacy of breast cancer metastasis. BMC Cancer. 2010 May 20;10:217.
DS RISalud
RD Apr 4, 2025