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The prognostic significance of serum and cerebrospinal fluid MMP-9, CCL2 and sVCAM-1 in leukemia CNS metastasis

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Abstract

Metastasis to the central nervous system (CNS) is the primary obstacle in leukemia treatment. Matrix metalloproteinase-9 (MMP-9), chemokine ligand-2 (CCL2) and soluble vascular adhesion molecule-1 (sVCAM-1) play crucial roles in tumor cell adhesion, motivation and survival, but their roles in leukemia CNS metastasis remain to be elucidated. We investigated the prognostic significance of serum and cerebrospinal fluid (CSF) MMP-9, CCL2 and sVCAM-1 in leukemia patients to explore their potential as predictive biomarkers of the development of CNS leukemia (CNSL). MMP-9, CCL2 and sVCAM-1 were measured in paired CSF and serum samples collecting from 33 leukemia patients with or without CNS metastasis. Other risk factors related to CNSL prognosis were also analyzed. sVCAM-1Serum and CCL2Serum/CSF were significantly higher in the CNSL group than in the non-CNSL group and the controls (p < 0.05). MMP-9Serum was insignificantly lower in the CNSL group than in the non-CNSL group and the controls (p > 0.05). No differences were found for the sVCAM-1Serum, CCL2Serum, and MMP-9Serum levels between non-CNSL patients and controls (p > 0.05). MMP-9CSF was significantly higher in the CNSL group than both the non-CNSL and the control groups (p < 0.05). The indexes of sVCAM-1, CCL2, and MMP-9 in the CNSL group were lower than in the controls (p < 0.05). Positive correlations were determined between the MMP-9CSF and the ALBCSF/BBB value/WBCCSF, between sVCAM-1Serum and the WBCCSF/BBB value. Negative correlations existed between MMP-9Serum and the ALBCSF/BBB value/WBCCSF, and between the CCL2 index and ALBCSF. sVCAM-1Serum was positively associated with event-free survival (EFS), and patients with higher levels of ALBCSF, MMP-9CSF/Serum, CCL2CSF/Serum, and sVCAM-1CSF/Serum had shorter EFS. MMP-9CSF, CCL2CSF and sVCAM-1CSF are the first three principal components analyzed by cluster and principal component analysis. Our data suggest that MMP-9, CCL2 and sVCAM-1 in the CSF may be more potent than serum in predicting the possibility of leukemia metastatic CNS and the outcome of CNSL patients.

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Acknowledgments

This study was funded by Natural Science Foundation of Guangdong Province, China (S2012030006289, NO9151008901000043), Science and Technology Program of Guangdong Province, China (Nos. 2010B031600321, and 2012B031800217).

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We declare that we have no conflicts of interest.

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Authors and Affiliations

  1. Department of Cell Biology and Genetics, Shantou University Medical College, 22 Xinling Road, Shantou, 515041, Guangdong, China

    Meng-Ya Si, Zhi-Cheng Fan, Ya-zhen Li, Xiao-Lan Chang, Qing-Dong Xie & Xiao-Yang Jiao

  2. Department of Cell Biology and Genetics, Key Laboratory of Molecular Biology in High Cancer Incidence Coastal ChaoShan Area of Guangdong Higher Education Institutes, Shantou University Medical College, Shantou, 515041, China

    Xiao-Lan Chang, Qing-Dong Xie & Xiao-Yang Jiao

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  1. Meng-Ya Si
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Si, MY., Fan, ZC., Li, Yz. et al. The prognostic significance of serum and cerebrospinal fluid MMP-9, CCL2 and sVCAM-1 in leukemia CNS metastasis. J Neurooncol 122, 229–244 (2015). https://doi.org/10.1007/s11060-014-1707-8

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