Decreased expression of angiogenesis antagonist EFEMP1 in sporadic breast cancer is caused by aberrant promoter methylation and points to an impact of EFEMP1 as molecular biomarker

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Item Type:	Article
Title:	Decreased expression of angiogenesis antagonist EFEMP1 in sporadic breast cancer is caused by aberrant promoter methylation and points to an impact of EFEMP1 as molecular biomarker
Creators Name:	Sadr-Nabavi, A., Ramser, J., Volkmann, J., Naehrig, J., Wiesmann, F., Betz, B., Hellebrand, H., Engert, S., Seitz, S., Kreutzfeld, R., Sasaki, T., Arnold, N., Schmutzler, R., Kiechle, M., Niederacher, D., Harbeck, N., Dahl, E. and Meindl, A.
Abstract:	EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1) was recently described as an antagonist of angiogenesis. Motivated by a strong dependence of tumor growth and metastasis on angiogenesis, we investigated the role of EFEMP1 in human breast cancer. We applied RNA microarray expression analysis and quantitative real-time PCR (QRT) in a total of 45 sporadic breast cancer tissues and found EFEMP1 down-regulation in 59% and 61% of the analyzed tissues, respectively. This down-regulation was confirmed on protein level. Immunohistochemistry in 211 breast cancer tissues resulted in reduced or even abolished EFEMP1 expression in 57-62.5% of the tumors. Bisulphite genomic sequencing in breast cancer cell lines and primary breast cancer tissues revealed promoter methylation as the major cause of this down-regulation. Furthermore, analysis of 203 clinically well characterized primary breast cancers displayed a significant correlation of reduced EFEMP1 protein expression with poor disease-free (p = 0.037) and overall survival (p = 0.032), particularly in those node-positive patients who received adjuvant anthracycline-based chemotherapy, but not in those treated by either cyclophosphamide-methotrexate-5-fluorouracil (CMF) or Tamoxifen. In summary, the presented data demonstrate for the first time the reduced EFEMP1 expression on RNA and protein level in a substantial number of sporadic breast carcinomas and its correlation with epigenetic alterations. Furthermore, these data point towards a possible predictive impact of EFEMP1 expression in primary breast cancer.
Keywords:	Breast Cancer, EFEMP1, Angiogenesis, Promoter Methylation, Molecular Marker
Source:	International Journal of Cancer
ISSN:	0020-7136
Publisher:	Wiley
Volume:	124
Number:	7
Page Range:	1727-1735
Date:	1 April 2009
Official Publication:	https://doi.org/10.1002/ijc.24108
PubMed:	View item in PubMed

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