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

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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

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Breast Neoplasms
Brain Neoplasms
Neoplasm Metastasis
Brain
Methylation
Neoplasms
Survival
Incidence
Gene Expression Profiling
Genes
Proteins
Multivariate Analysis
Lymph Nodes
Gene Expression
Recurrence
Cell Line
Polymerase Chain Reaction

Keywords

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

Cite this

Wikman, H., Westphal, L., Schmid, F., Pollari, S., Kropidlowski, J., Sielaff-Frimpong, B., ... Pantel, K. (2014). Loss of CADM1 expression is associated with poor prognosis and brain metastasis in breast cancer patients. Oncotarget, 5(10), 3076-3087. https://doi.org/10.18632/oncotarget.1832
Wikman, H. ; Westphal, L. ; Schmid, F. ; Pollari, Sirkku ; Kropidlowski, J. ; Sielaff-Frimpong, B. ; Glatzel, M. ; Matschke, J. ; Westphal, M. ; Iljin, Kristiina ; Huhtala, H. ; Terraciano, L. ; Kallioniemi, A. ; Sauter, G. ; Müller, V. ; Witzel, I. ; Lamszus, K. ; Kemming, D. ; Pantel, K. / Loss of CADM1 expression is associated with poor prognosis and brain metastasis in breast cancer patients. In: Oncotarget. 2014 ; Vol. 5, No. 10. pp. 3076-3087.
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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.",
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author = "H. Wikman and L. Westphal and F. Schmid and Sirkku Pollari and J. Kropidlowski and B. Sielaff-Frimpong and M. Glatzel and J. Matschke and M. Westphal and Kristiina Iljin and H. Huhtala and L. Terraciano and A. Kallioniemi and G. Sauter and V. M{\"u}ller and I. Witzel and K. Lamszus and D. Kemming and K. Pantel",
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Wikman, H, Westphal, L, Schmid, F, Pollari, S, Kropidlowski, J, Sielaff-Frimpong, B, Glatzel, M, Matschke, J, Westphal, M, Iljin, K, Huhtala, H, Terraciano, L, Kallioniemi, A, Sauter, G, Müller, V, Witzel, I, Lamszus, K, Kemming, D & Pantel, K 2014, 'Loss of CADM1 expression is associated with poor prognosis and brain metastasis in breast cancer patients', Oncotarget, vol. 5, no. 10, pp. 3076-3087. https://doi.org/10.18632/oncotarget.1832

Loss of CADM1 expression is associated with poor prognosis and brain metastasis in breast cancer patients. / Wikman, H. (Corresponding Author); Westphal, L.; Schmid, F.; Pollari, Sirkku; Kropidlowski, J.; Sielaff-Frimpong, B.; Glatzel, M.; Matschke, J.; Westphal, M.; Iljin, Kristiina; Huhtala, H.; Terraciano, L.; Kallioniemi, A.; Sauter, G.; Müller, V.; Witzel, I.; Lamszus, K.; Kemming, D.; Pantel, K.

In: Oncotarget, Vol. 5, No. 10, 2014, p. 3076-3087.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Loss of CADM1 expression is associated with poor prognosis and brain metastasis in breast cancer patients

AU - Wikman, H.

AU - Westphal, L.

AU - Schmid, F.

AU - Pollari, Sirkku

AU - Kropidlowski, J.

AU - Sielaff-Frimpong, B.

AU - Glatzel, M.

AU - Matschke, J.

AU - Westphal, M.

AU - Iljin, Kristiina

AU - Huhtala, H.

AU - Terraciano, L.

AU - Kallioniemi, A.

AU - Sauter, G.

AU - Müller, V.

AU - Witzel, I.

AU - Lamszus, K.

AU - Kemming, D.

AU - Pantel, K.

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - breast cancer

KW - brain metastases

KW - CADM1

KW - methylation

KW - genes

U2 - 10.18632/oncotarget.1832

DO - 10.18632/oncotarget.1832

M3 - Article

VL - 5

SP - 3076

EP - 3087

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 10

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Wikman H, Westphal L, Schmid F, Pollari S, Kropidlowski J, Sielaff-Frimpong B et al. Loss of CADM1 expression is associated with poor prognosis and brain metastasis in breast cancer patients. Oncotarget. 2014;5(10):3076-3087. https://doi.org/10.18632/oncotarget.1832