Abstract

Simple SummaryCartilage oligomeric matrix protein (COMP) is an emerging independent prognostic marker for breast cancer patients. COMP expression by cancer cells affects their metabolism, metastases, and the abundance of cancer stem cell populations. This study assessed the levels of COMP in the sera of metastatic breast cancer patients. Further, matched tumor tissues from the primary tumor and metastases were stained for COMP expression with immunohistochemistry. The levels of serum COMP were highest in the blood of metastatic ER-positive and HER2-positive patients. The expression of COMP in primary tumors correlated with COMP expression in the metastatic loci. Lymph node metastases (LNM) with COMP expression were associated with reduced survival. The expression of COMP in LNM at the time of primary diagnosis could indicate later development of visceral and lung metastases.Cartilage oligomeric matrix protein (COMP) is a regulator of the extracellular matrix and is expressed primarily in the cartilage. Recently, COMP expression was also documented in breast cancer patients both in sera and tumor biopsies, in both of which it could serve as an independent prognostic marker. This study aimed to assess COMP as a potential biomarker in the group of metastatic breast cancer patients. Levels of COMP were measured by ELISA in serum samples of 141 metastatic breast cancer patients. Biopsies from primary tumors, synchronous lymph node metastases, and distant metastases were stained for COMP expression. The levels of serum COMP were higher in patients with ER- and HER2-positive tumors when compared to triple-negative tumors and correlated with the presence of bone and lung metastases, circulating tumor cell count, and clusters. Most of the primary tumors expressing COMP (70%) retained the expression also in the lymph node metastases, which correlated with visceral metastases and reduced survival. In conclusion, COMP appears as a valuable biomarker in metastatic breast cancer patients indicating a more severe stage of the disease. Serum COMP levels were associated with specific types of metastases in patients with metastatic breast cancer emphasizing that further studies are warranted to elucidate its potential role as a monitoring marker.

Highlights

  • Cartilage oligomeric matrix protein (COMP) has been traditionally viewed as an extracellular matrix (ECM) protein that is expressed by chondrocytes of cartilage [1] as well as fibroblasts under fibrotic conditions [2] and contributes to the organization of ECM [3].COMP is known as thrombospondin 5, belonging to the thrombospondin family [4]

  • We found increased levels of COMP in sera of metastatic breast cancer (MBC) patients compared with those with early breast cancer

  • High S-COMP levels were associated with HER2-positive and ER-positive disease whereas low S-COMP levels were seen in patients with triple-negative breast cancer (TNBC)

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Summary

Introduction

Cartilage oligomeric matrix protein (COMP) has been traditionally viewed as an extracellular matrix (ECM) protein that is expressed by chondrocytes of cartilage [1] as well as fibroblasts under fibrotic conditions [2] and contributes to the organization of ECM [3]. COMP is known as thrombospondin 5, belonging to the thrombospondin family [4]. Several new functions have been ascribed to this large, pentameric molecule. COMP was shown to contribute to vascular homeostasis since its degradation by ADAMTS-7 [5] regulates vascular remodeling. COMP has been found in atherosclerotic plaques [6] and lesions contributing to restenosis of the artery [7]. COMP inhibits thrombin [8] and can act as a regulator of the complement system [9,10]

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