Bone metastasis-related signaling pathways in breast cancers stratified by estrogen receptor status

Naoki Hayashi, Takayuki Iwamoto, Yuan Qi, Naoki Niikura, Libero Santarpia, Hideko Yamauchi, Seigo Nakamura, Gabriel N. Hortobagyi, Lajos Pusztai, W. Fraser Symmans, Naoto T. Ueno

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: Breast cancer bone metastasis (BCBM)-specific genes have been reported without considering biological differences based on estrogen receptor (ER) status. The aims of this study were to identify BCBM-specific genes using our patient dataset and validate previously reported BCBM-specific genes, and to determine whether ER-status-related biological differences matter in identification of BCBM-specific genes. Methods: We used Affymetrix GeneChips to analyze 365 primary human epidermal growth factor receptor 2 (HER2)-negative invasive breast cancer specimens. Genes that were differentially expressed between patients who developed bone metastasis and those who developed non-bone metastasis were identified using Cox proportional hazards model, and differential expression of gene sets was assessed using gene set analysis. We performed gene set analysis to determine whether biological function associated with bone metastasis were different by ER status using 2,246 functionally annotated gene sets assembled from Gene Ontology data base. Results: Among 16,712 probe sets, 592 were overexpressed in the bone metastasis cohort compared to the non-bone-metastasis cohort (false discovery rate = 0.05). However, no BCBM-specific genes met our significance tests when the cancers were stratified by ER status. In ER-positive and ER-negative breast cancers, 151 and 125 gene sets, respectively, were overexpressed for BCBM and the majority of BCBM-related pathways were different. Of significant gene sets, only 13 gene sets were overlapped between ER-positive and -negative cohorts. Conclusion: ER-positive and ER-negative breast cancers have different biological pathways in BCBM development. We have yet to explore BCBM-related biomarkers and targets considering the biological features associated with BCBM depending on the ER status.

Original languageEnglish
Pages (from-to)1045-1052
Number of pages8
JournalJournal of Cancer
Volume8
Issue number6
DOIs
Publication statusPublished - Apr 9 2017
Externally publishedYes

Fingerprint

Estrogen Receptors
Bone Neoplasms
Breast Neoplasms
Neoplasm Metastasis
Bone and Bones
Genes
Gene Ontology
Bone Development
Proportional Hazards Models
Biomarkers

Keywords

  • Bone metastasis
  • Breast cancer
  • Estrogen receptor status
  • Gene expression
  • Gene sets

ASJC Scopus subject areas

  • Oncology

Cite this

Hayashi, N., Iwamoto, T., Qi, Y., Niikura, N., Santarpia, L., Yamauchi, H., ... Ueno, N. T. (2017). Bone metastasis-related signaling pathways in breast cancers stratified by estrogen receptor status. Journal of Cancer, 8(6), 1045-1052. https://doi.org/10.7150/jca.13690

Bone metastasis-related signaling pathways in breast cancers stratified by estrogen receptor status. / Hayashi, Naoki; Iwamoto, Takayuki; Qi, Yuan; Niikura, Naoki; Santarpia, Libero; Yamauchi, Hideko; Nakamura, Seigo; Hortobagyi, Gabriel N.; Pusztai, Lajos; Fraser Symmans, W.; Ueno, Naoto T.

In: Journal of Cancer, Vol. 8, No. 6, 09.04.2017, p. 1045-1052.

Research output: Contribution to journalArticle

Hayashi, N, Iwamoto, T, Qi, Y, Niikura, N, Santarpia, L, Yamauchi, H, Nakamura, S, Hortobagyi, GN, Pusztai, L, Fraser Symmans, W & Ueno, NT 2017, 'Bone metastasis-related signaling pathways in breast cancers stratified by estrogen receptor status', Journal of Cancer, vol. 8, no. 6, pp. 1045-1052. https://doi.org/10.7150/jca.13690
Hayashi, Naoki ; Iwamoto, Takayuki ; Qi, Yuan ; Niikura, Naoki ; Santarpia, Libero ; Yamauchi, Hideko ; Nakamura, Seigo ; Hortobagyi, Gabriel N. ; Pusztai, Lajos ; Fraser Symmans, W. ; Ueno, Naoto T. / Bone metastasis-related signaling pathways in breast cancers stratified by estrogen receptor status. In: Journal of Cancer. 2017 ; Vol. 8, No. 6. pp. 1045-1052.
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title = "Bone metastasis-related signaling pathways in breast cancers stratified by estrogen receptor status",
abstract = "Background: Breast cancer bone metastasis (BCBM)-specific genes have been reported without considering biological differences based on estrogen receptor (ER) status. The aims of this study were to identify BCBM-specific genes using our patient dataset and validate previously reported BCBM-specific genes, and to determine whether ER-status-related biological differences matter in identification of BCBM-specific genes. Methods: We used Affymetrix GeneChips to analyze 365 primary human epidermal growth factor receptor 2 (HER2)-negative invasive breast cancer specimens. Genes that were differentially expressed between patients who developed bone metastasis and those who developed non-bone metastasis were identified using Cox proportional hazards model, and differential expression of gene sets was assessed using gene set analysis. We performed gene set analysis to determine whether biological function associated with bone metastasis were different by ER status using 2,246 functionally annotated gene sets assembled from Gene Ontology data base. Results: Among 16,712 probe sets, 592 were overexpressed in the bone metastasis cohort compared to the non-bone-metastasis cohort (false discovery rate = 0.05). However, no BCBM-specific genes met our significance tests when the cancers were stratified by ER status. In ER-positive and ER-negative breast cancers, 151 and 125 gene sets, respectively, were overexpressed for BCBM and the majority of BCBM-related pathways were different. Of significant gene sets, only 13 gene sets were overlapped between ER-positive and -negative cohorts. Conclusion: ER-positive and ER-negative breast cancers have different biological pathways in BCBM development. We have yet to explore BCBM-related biomarkers and targets considering the biological features associated with BCBM depending on the ER status.",
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author = "Naoki Hayashi and Takayuki Iwamoto and Yuan Qi and Naoki Niikura and Libero Santarpia and Hideko Yamauchi and Seigo Nakamura and Hortobagyi, {Gabriel N.} and Lajos Pusztai and {Fraser Symmans}, W. and Ueno, {Naoto T.}",
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T1 - Bone metastasis-related signaling pathways in breast cancers stratified by estrogen receptor status

AU - Hayashi, Naoki

AU - Iwamoto, Takayuki

AU - Qi, Yuan

AU - Niikura, Naoki

AU - Santarpia, Libero

AU - Yamauchi, Hideko

AU - Nakamura, Seigo

AU - Hortobagyi, Gabriel N.

AU - Pusztai, Lajos

AU - Fraser Symmans, W.

AU - Ueno, Naoto T.

PY - 2017/4/9

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N2 - Background: Breast cancer bone metastasis (BCBM)-specific genes have been reported without considering biological differences based on estrogen receptor (ER) status. The aims of this study were to identify BCBM-specific genes using our patient dataset and validate previously reported BCBM-specific genes, and to determine whether ER-status-related biological differences matter in identification of BCBM-specific genes. Methods: We used Affymetrix GeneChips to analyze 365 primary human epidermal growth factor receptor 2 (HER2)-negative invasive breast cancer specimens. Genes that were differentially expressed between patients who developed bone metastasis and those who developed non-bone metastasis were identified using Cox proportional hazards model, and differential expression of gene sets was assessed using gene set analysis. We performed gene set analysis to determine whether biological function associated with bone metastasis were different by ER status using 2,246 functionally annotated gene sets assembled from Gene Ontology data base. Results: Among 16,712 probe sets, 592 were overexpressed in the bone metastasis cohort compared to the non-bone-metastasis cohort (false discovery rate = 0.05). However, no BCBM-specific genes met our significance tests when the cancers were stratified by ER status. In ER-positive and ER-negative breast cancers, 151 and 125 gene sets, respectively, were overexpressed for BCBM and the majority of BCBM-related pathways were different. Of significant gene sets, only 13 gene sets were overlapped between ER-positive and -negative cohorts. Conclusion: ER-positive and ER-negative breast cancers have different biological pathways in BCBM development. We have yet to explore BCBM-related biomarkers and targets considering the biological features associated with BCBM depending on the ER status.

AB - Background: Breast cancer bone metastasis (BCBM)-specific genes have been reported without considering biological differences based on estrogen receptor (ER) status. The aims of this study were to identify BCBM-specific genes using our patient dataset and validate previously reported BCBM-specific genes, and to determine whether ER-status-related biological differences matter in identification of BCBM-specific genes. Methods: We used Affymetrix GeneChips to analyze 365 primary human epidermal growth factor receptor 2 (HER2)-negative invasive breast cancer specimens. Genes that were differentially expressed between patients who developed bone metastasis and those who developed non-bone metastasis were identified using Cox proportional hazards model, and differential expression of gene sets was assessed using gene set analysis. We performed gene set analysis to determine whether biological function associated with bone metastasis were different by ER status using 2,246 functionally annotated gene sets assembled from Gene Ontology data base. Results: Among 16,712 probe sets, 592 were overexpressed in the bone metastasis cohort compared to the non-bone-metastasis cohort (false discovery rate = 0.05). However, no BCBM-specific genes met our significance tests when the cancers were stratified by ER status. In ER-positive and ER-negative breast cancers, 151 and 125 gene sets, respectively, were overexpressed for BCBM and the majority of BCBM-related pathways were different. Of significant gene sets, only 13 gene sets were overlapped between ER-positive and -negative cohorts. Conclusion: ER-positive and ER-negative breast cancers have different biological pathways in BCBM development. We have yet to explore BCBM-related biomarkers and targets considering the biological features associated with BCBM depending on the ER status.

KW - Bone metastasis

KW - Breast cancer

KW - Estrogen receptor status

KW - Gene expression

KW - Gene sets

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