Circulating Osteocalcin-Positive Cells as a Novel Diagnostic Biomarker for Bone Metastasis in Breast Cancer Patients

Kyung Hun Lee; Kyoung Jin Lee; Tae Yong Kim; Febby Hutomo; Hyun Jin Sun; Gi Jeong Cheon; Serk In Park; Sun Wook Cho; Seock Ah Im

doi:10.1002/jbmr.4041

Circulating Osteocalcin-Positive Cells as a Novel Diagnostic Biomarker for Bone Metastasis in Breast Cancer Patients

Kyung Hun Lee, Kyoung Jin Lee, Tae Yong Kim, Febby Hutomo, Hyun Jin Sun, Gi Jeong Cheon, Serk In Park, Sun Wook Cho, Seock Ah Im

Department of Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

13 Citations (Scopus)

Abstract

Current diagnosis of bone metastasis (BM) in breast cancer relies on structural changes of bone that occur only in the advanced stage. A sensitive biomarker for detecting early progression of bone metastasis is urgently required. We performed clinical and preclinical studies to investigate diagnostic value of circulating osteocalcin-positive cells (cOC) in breast cancer bone metastasis. Metastatic breast cancer patients (n = 92) with or without bone metastasis (ie, BM⁺ or BM^–) were enrolled, and cOC were measured at enrollment. Patients were followed up for bone metastasis progression for 18 months. BM⁺ patients (n = 59) were divided into progressive (PD) or stable disease (SD) groups, based on imaging studies at the end of the 18-month study. The PD group had higher baseline cOC compared with the SD group. Furthermore, higher cOC resulted in reduced BM progression-free survival. Three patients in the BM^– group (n = 33) developed new BM during the 18-month study, and these patients had a higher level of baseline cOC compared with the remaining BM^– patients. In murine preclinical studies, cOC increased at early time points when micro-metastases were evident only by histology but undetectable by bioluminescence imaging. Also, cOC levels predicted the progression of BM and correlated significantly with BM tumor burden. cOC increased in the early phase of breast cancer BM and can predict BM progression, supporting cOC as a potential novel biomarker.

Original language	English
Pages (from-to)	1838-1849
Number of pages	12
Journal	Journal of Bone and Mineral Research
Volume	35
Issue number	10
DOIs	https://doi.org/10.1002/jbmr.4041
Publication status	Published - 2020 Oct 1

Bibliographical note

Funding Information:
The authors thank Cytogen, Inc. for assistance with cell size measurement. The authors thank Dr Juneyoung Lee in the Department of Biostatistics, Korea University College of Medicine, Seoul, South Korea, for statistical consultation. This study was supported by a grant from the National R&D Program for Cancer Control, the Ministry of Health and Welfare, the Republic of Korea (HA17C0040). Authors’ roles: Study design: SIP and SWC. Clinical data collection and interpretation: KHL, TYK, SWC and SAI. Clinical imaging study: FH, GJC and SWC. Flow cytometry and in vivo experiments: KJL, HJS, SIP and SWC. Data analysis and interpretation: SIP and SWC. Drafting manuscript: KHL, KJL, SIP and SWC. Revising manuscript: KHL, SIP and SWC. All authors approved the final manuscript.

Funding Information:
This study was supported by a grant from the National R&D Program for Cancer Control, the Ministry of Health and Welfare, the Republic of Korea (HA17C0040).

Publisher Copyright:
© 2020 American Society for Bone and Mineral Research

Keywords

BIOMARKER
BONE METASTASIS
BREAST CANCER
OSTEOBLASTS
OSTEOCALCIN

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Orthopedics and Sports Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/jbmr.4041

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title = "Circulating Osteocalcin-Positive Cells as a Novel Diagnostic Biomarker for Bone Metastasis in Breast Cancer Patients",

abstract = "Current diagnosis of bone metastasis (BM) in breast cancer relies on structural changes of bone that occur only in the advanced stage. A sensitive biomarker for detecting early progression of bone metastasis is urgently required. We performed clinical and preclinical studies to investigate diagnostic value of circulating osteocalcin-positive cells (cOC) in breast cancer bone metastasis. Metastatic breast cancer patients (n = 92) with or without bone metastasis (ie, BM+ or BM–) were enrolled, and cOC were measured at enrollment. Patients were followed up for bone metastasis progression for 18 months. BM+ patients (n = 59) were divided into progressive (PD) or stable disease (SD) groups, based on imaging studies at the end of the 18-month study. The PD group had higher baseline cOC compared with the SD group. Furthermore, higher cOC resulted in reduced BM progression-free survival. Three patients in the BM– group (n = 33) developed new BM during the 18-month study, and these patients had a higher level of baseline cOC compared with the remaining BM– patients. In murine preclinical studies, cOC increased at early time points when micro-metastases were evident only by histology but undetectable by bioluminescence imaging. Also, cOC levels predicted the progression of BM and correlated significantly with BM tumor burden. cOC increased in the early phase of breast cancer BM and can predict BM progression, supporting cOC as a potential novel biomarker.",

keywords = "BIOMARKER, BONE METASTASIS, BREAST CANCER, OSTEOBLASTS, OSTEOCALCIN",

author = "Lee, {Kyung Hun} and Lee, {Kyoung Jin} and Kim, {Tae Yong} and Febby Hutomo and Sun, {Hyun Jin} and Cheon, {Gi Jeong} and Park, {Serk In} and Cho, {Sun Wook} and Im, {Seock Ah}",

note = "Funding Information: The authors thank Cytogen, Inc. for assistance with cell size measurement. The authors thank Dr Juneyoung Lee in the Department of Biostatistics, Korea University College of Medicine, Seoul, South Korea, for statistical consultation. This study was supported by a grant from the National R&D Program for Cancer Control, the Ministry of Health and Welfare, the Republic of Korea (HA17C0040). Authors{\textquoteright} roles: Study design: SIP and SWC. Clinical data collection and interpretation: KHL, TYK, SWC and SAI. Clinical imaging study: FH, GJC and SWC. Flow cytometry and in vivo experiments: KJL, HJS, SIP and SWC. Data analysis and interpretation: SIP and SWC. Drafting manuscript: KHL, KJL, SIP and SWC. Revising manuscript: KHL, SIP and SWC. All authors approved the final manuscript. Funding Information: This study was supported by a grant from the National R&D Program for Cancer Control, the Ministry of Health and Welfare, the Republic of Korea (HA17C0040). Publisher Copyright: {\textcopyright} 2020 American Society for Bone and Mineral Research",

year = "2020",

month = oct,

day = "1",

doi = "10.1002/jbmr.4041",

language = "English",

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pages = "1838--1849",

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T1 - Circulating Osteocalcin-Positive Cells as a Novel Diagnostic Biomarker for Bone Metastasis in Breast Cancer Patients

AU - Lee, Kyung Hun

AU - Lee, Kyoung Jin

AU - Kim, Tae Yong

AU - Hutomo, Febby

AU - Sun, Hyun Jin

AU - Cheon, Gi Jeong

AU - Park, Serk In

AU - Cho, Sun Wook

AU - Im, Seock Ah

N1 - Funding Information: The authors thank Cytogen, Inc. for assistance with cell size measurement. The authors thank Dr Juneyoung Lee in the Department of Biostatistics, Korea University College of Medicine, Seoul, South Korea, for statistical consultation. This study was supported by a grant from the National R&D Program for Cancer Control, the Ministry of Health and Welfare, the Republic of Korea (HA17C0040). Authors’ roles: Study design: SIP and SWC. Clinical data collection and interpretation: KHL, TYK, SWC and SAI. Clinical imaging study: FH, GJC and SWC. Flow cytometry and in vivo experiments: KJL, HJS, SIP and SWC. Data analysis and interpretation: SIP and SWC. Drafting manuscript: KHL, KJL, SIP and SWC. Revising manuscript: KHL, SIP and SWC. All authors approved the final manuscript. Funding Information: This study was supported by a grant from the National R&D Program for Cancer Control, the Ministry of Health and Welfare, the Republic of Korea (HA17C0040). Publisher Copyright: © 2020 American Society for Bone and Mineral Research

PY - 2020/10/1

Y1 - 2020/10/1

N2 - Current diagnosis of bone metastasis (BM) in breast cancer relies on structural changes of bone that occur only in the advanced stage. A sensitive biomarker for detecting early progression of bone metastasis is urgently required. We performed clinical and preclinical studies to investigate diagnostic value of circulating osteocalcin-positive cells (cOC) in breast cancer bone metastasis. Metastatic breast cancer patients (n = 92) with or without bone metastasis (ie, BM+ or BM–) were enrolled, and cOC were measured at enrollment. Patients were followed up for bone metastasis progression for 18 months. BM+ patients (n = 59) were divided into progressive (PD) or stable disease (SD) groups, based on imaging studies at the end of the 18-month study. The PD group had higher baseline cOC compared with the SD group. Furthermore, higher cOC resulted in reduced BM progression-free survival. Three patients in the BM– group (n = 33) developed new BM during the 18-month study, and these patients had a higher level of baseline cOC compared with the remaining BM– patients. In murine preclinical studies, cOC increased at early time points when micro-metastases were evident only by histology but undetectable by bioluminescence imaging. Also, cOC levels predicted the progression of BM and correlated significantly with BM tumor burden. cOC increased in the early phase of breast cancer BM and can predict BM progression, supporting cOC as a potential novel biomarker.

AB - Current diagnosis of bone metastasis (BM) in breast cancer relies on structural changes of bone that occur only in the advanced stage. A sensitive biomarker for detecting early progression of bone metastasis is urgently required. We performed clinical and preclinical studies to investigate diagnostic value of circulating osteocalcin-positive cells (cOC) in breast cancer bone metastasis. Metastatic breast cancer patients (n = 92) with or without bone metastasis (ie, BM+ or BM–) were enrolled, and cOC were measured at enrollment. Patients were followed up for bone metastasis progression for 18 months. BM+ patients (n = 59) were divided into progressive (PD) or stable disease (SD) groups, based on imaging studies at the end of the 18-month study. The PD group had higher baseline cOC compared with the SD group. Furthermore, higher cOC resulted in reduced BM progression-free survival. Three patients in the BM– group (n = 33) developed new BM during the 18-month study, and these patients had a higher level of baseline cOC compared with the remaining BM– patients. In murine preclinical studies, cOC increased at early time points when micro-metastases were evident only by histology but undetectable by bioluminescence imaging. Also, cOC levels predicted the progression of BM and correlated significantly with BM tumor burden. cOC increased in the early phase of breast cancer BM and can predict BM progression, supporting cOC as a potential novel biomarker.

KW - BIOMARKER

KW - BONE METASTASIS

KW - BREAST CANCER

KW - OSTEOBLASTS

KW - OSTEOCALCIN

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Circulating Osteocalcin-Positive Cells as a Novel Diagnostic Biomarker for Bone Metastasis in Breast Cancer Patients

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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