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

H. Wikman (Corresponding Author), L. Westphal, F. Schmid, Sirkku Pollari, J. Kropidlowski, B. Sielaff-Frimpong, M. Glatzel, J. Matschke, M. Westphal, Kristiina Iljin, H. Huhtala, L. Terraciano, A. Kallioniemi, G. Sauter, V. Müller, I. Witzel, K. Lamszus, D. Kemming, K. Pantel

    Research output: Contribution to journalArticleScientificpeer-review

    27 Citations (Scopus)

    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.
    Original languageEnglish
    Pages (from-to)3076-3087
    Number of pages12
    JournalOncotarget
    Volume5
    Issue number10
    DOIs
    Publication statusPublished - 2014
    MoE publication typeA1 Journal article-refereed

    Keywords

    • breast cancer
    • brain metastases
    • CADM1
    • methylation
    • genes

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