Hypermethylated <it>14-3-3-σ </it>and <it>ESR1 </it>gene promoters in serum as candidate biomarkers for the diagnosis and treatment efficacy of breast cancer metastasis
<p>Abstract</p> <p>Background</p> <p>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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2010-05-01
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| Series: | BMC Cancer |
| Online Access: | http://www.biomedcentral.com/1471-2407/10/217 |
| _version_ | 1818582028749111296 |
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| author | Martínez-Galán Joaquina Arrabal Sandra Linares-Fernández José Torres Blanca del Moral Rosario Zurita Mercedes Lara Pedro C Oliver Francisco Ruiz de Almodóvar José |
| author_facet | Martínez-Galán Joaquina Arrabal Sandra Linares-Fernández José Torres Blanca del Moral Rosario Zurita Mercedes Lara Pedro C Oliver Francisco Ruiz de Almodóvar José |
| author_sort | Martínez-Galán Joaquina |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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 <it>Estrogen Receptor1 </it>(<it>ESR1</it>) and <it>Stratifin </it>(<it>14-3-3-σ</it>) gene promoters in disease-free and metastatic breast cancer patients.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>Serum levels of methylated gene promoter <it>14-3-3-σ </it>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 <it>14-3-3-σ </it>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.</p> <p>Conclusions</p> <p>The relationship of <it>14-3-3-σ </it>with breast cancer metastasis and progression found in this study suggests a possible application of <it>14-3-3-σ </it>as a biomarker to screen for metastasis and to follow up patients treated for metastatic breast cancer, monitoring their disease status and treatment response.</p> |
| first_indexed | 2024-12-16T07:42:53Z |
| format | Article |
| id | doaj.art-4ef24788888d462c88d3b4736d6cc16d |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-16T07:42:53Z |
| publishDate | 2010-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-4ef24788888d462c88d3b4736d6cc16d2022-12-21T22:39:02ZengBMCBMC Cancer1471-24072010-05-0110121710.1186/1471-2407-10-217Hypermethylated <it>14-3-3-σ </it>and <it>ESR1 </it>gene promoters in serum as candidate biomarkers for the diagnosis and treatment efficacy of breast cancer metastasisMartínez-Galán JoaquinaArrabal SandraLinares-Fernández JoséTorres Blancadel Moral RosarioZurita MercedesLara Pedro COliver FranciscoRuiz de Almodóvar José<p>Abstract</p> <p>Background</p> <p>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 <it>Estrogen Receptor1 </it>(<it>ESR1</it>) and <it>Stratifin </it>(<it>14-3-3-σ</it>) gene promoters in disease-free and metastatic breast cancer patients.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>Serum levels of methylated gene promoter <it>14-3-3-σ </it>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 <it>14-3-3-σ </it>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.</p> <p>Conclusions</p> <p>The relationship of <it>14-3-3-σ </it>with breast cancer metastasis and progression found in this study suggests a possible application of <it>14-3-3-σ </it>as a biomarker to screen for metastasis and to follow up patients treated for metastatic breast cancer, monitoring their disease status and treatment response.</p>http://www.biomedcentral.com/1471-2407/10/217 |
| spellingShingle | Martínez-Galán Joaquina Arrabal Sandra Linares-Fernández José Torres Blanca del Moral Rosario Zurita Mercedes Lara Pedro C Oliver Francisco Ruiz de Almodóvar José Hypermethylated <it>14-3-3-σ </it>and <it>ESR1 </it>gene promoters in serum as candidate biomarkers for the diagnosis and treatment efficacy of breast cancer metastasis BMC Cancer |
| title | Hypermethylated <it>14-3-3-σ </it>and <it>ESR1 </it>gene promoters in serum as candidate biomarkers for the diagnosis and treatment efficacy of breast cancer metastasis |
| title_full | Hypermethylated <it>14-3-3-σ </it>and <it>ESR1 </it>gene promoters in serum as candidate biomarkers for the diagnosis and treatment efficacy of breast cancer metastasis |
| title_fullStr | Hypermethylated <it>14-3-3-σ </it>and <it>ESR1 </it>gene promoters in serum as candidate biomarkers for the diagnosis and treatment efficacy of breast cancer metastasis |
| title_full_unstemmed | Hypermethylated <it>14-3-3-σ </it>and <it>ESR1 </it>gene promoters in serum as candidate biomarkers for the diagnosis and treatment efficacy of breast cancer metastasis |
| title_short | Hypermethylated <it>14-3-3-σ </it>and <it>ESR1 </it>gene promoters in serum as candidate biomarkers for the diagnosis and treatment efficacy of breast cancer metastasis |
| title_sort | hypermethylated it 14 3 3 σ it and it esr1 it gene promoters in serum as candidate biomarkers for the diagnosis and treatment efficacy of breast cancer metastasis |
| url | http://www.biomedcentral.com/1471-2407/10/217 |
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