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Loss of CADM1 expression is associated with poor prognosis and brain metastasis in breast cancer patients

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Item Type:Article
Title:Loss of CADM1 expression is associated with poor prognosis and brain metastasis in breast cancer patients
Creators Name:Wikman, H. and Westphal, L. and Schmid, F. and Pollari, S. and Kropidlowski, J. and Sielaff-Frimpong, B. and Glatzel, M. and Matschke, J. and Westphal, M. and Iljin, K. and Huhtala, H. and Terracciano, L. and Kallioniemi, A. and Sauter, G. and Mueller, V. and Witzel, I. and Lamszus, K. and Kemming, D. and Pantel, K.
Abstract:Breast cancer brain metastases (BCBM) are detected with increasing incidence. In order to detect potential genes involved in BCBM, we first screened for genes down-regulated by methylation in cell lines with site-specific metastatic ability. The expression of five genes, CADM1, SPARC, RECK, TNFAIP3 and CXCL14, which were also found down-regulated in gene expression profiling analyses of BCBM tissue samples, was verified by qRT-PCR in a larger patient cohort. CADM1 was chosen for further down-stream analyses. A higher incidence of CADM1 methylation, correlating with lower expression levels, was found in BCBM as compared to primary BC. Loss of CADM1 protein expression was detected most commonly among BCBM samples as well as among primary tumors with subsequent brain relapse. The prognostic role of CADM1 expression was finally verified in four large independent breast cancer cohorts (n=2136). Loss of CADM1 protein expression was associated with disease stage, lymph node status, and tumor size in primary BC. Furthermore, all analyses revealed a significant association between loss of CADM1 and shorter survival. In multivariate analyses, survival was significantly shorter among patients with CADM1-negative tumors. Loss of CADM1 expression is an independent prognostic factor especially associated with the development of brain metastases in breast cancer patients.
Keywords:Breast Cancer, Brain Metastases, CADM1, Methylation
Source:Oncotarget
ISSN:1949-2553
Publisher:Impact Journals (U.S.A.)
Volume:5
Number:10
Page Range:3076-3087
Date:30 May 2014
Official Publication:http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=1832
PubMed:View item in PubMed

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