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J Cancer 2017; 8(17):3522-3530. doi:10.7150/jca.20227 This issue Cite

Research Paper

Combination of plasma HA and circulating M2-like monocytes may serve as a diagnostic marker for breast cancer

Boke Zhang^1*, Manlin Cao^2*, Yiqing He¹, Yiwen Liu¹, Guoliang Zhang¹, Cuixia Yang¹, Yan Du¹, Jing Xu³, Jiajie Hu¹, Feng Gao^4✉

1. Department of Molecular Biology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, PR China;
2. Department of Rehabilitation Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, PR China;
3. Department of Clinical Laboratory, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, PR China;
4. Department of Molecular Biology and Clinical Laboratory, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, PR China.
* Both are co-first authors

✉ Corresponding author: Feng Gao, Department of Molecular Biology and Clinical Laboratory, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, PR China. Tel: +86-21-64369181; Fax: +86-21-63701361; E-mail: gao3507com

Abstract

Background: Breast cancer (BC)-derived hyaluronan (HA) can induce the formation of M2-like tumor-associated macrophages (TAMs) in tumor context. However, little is known about the correlation between circulating M2-like monocytes and plasma HA in BC patients. This study focused on evaluating the relationship between circulating M2-like monocytes and plasma HA, and further appraised the diagnostic value of them in BC.

Methods: The expression of M2-like TAMs and HA was determined in pathological tissues by immunohistochemistry. Flow cytometry was used to detect the levels of circulating CD14⁺CD204⁺ M2-like monocytes in 81 BC patients, 45 patients with breast benign diseases, and 46 healthy subjects. The levels of HA, CEA, and CA15-3 were measured in plasma samples using chemiluminescence method.

Results: M2-like TAMs and HA expressions were elevated in BC tissues compared with benign tissues. In correspondence, the frequency of circulating CD14⁺CD204⁺ M2-like monocytes and the plasma HA levels were significantly higher in patients with BC than those in control groups. Importantly, there was a positive correlation between circulating M2-like monocytes and the plasma HA (Spearman r = 0.404, p < 0.001). Area under receiver operating characteristic curve (ROC) for the combination of circulating M2-like monocytes and HA was 0.899 (95% CI: 0.853-0.946), which was higher than the panel of CEA and CA15-3.

Conclusions: The frequency of circulating CD14⁺CD204⁺ M2-like monocytes was positively correlated to plasma HA levels. The combination of circulating CD14⁺CD204⁺ M2-like monocytes and plasma HA could provide considerable diagnostic value in BC.

Keywords: Breast cancer, CD163, CD204, biomarker, diagnosis

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