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

摘要

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-1(Serum) and CCL2(Serum/CSF) were significantly higher in the CNSL group than in the non-CNSL group and the controls (p < 0.05). MMP-9(Serum) 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-1(Serum), CCL2(Serum), and MMP-9(Serum) levels between non-CNSL patients and controls (p > 0.05). MMP-9(CSF) 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-9(CSF) and the ALB(CSF)/BBB value/WBCCSF, between sVCAM-1(Serum) and the WBCCSF/BBB value. Negative correlations existed between MMP-9(Serum) and the ALB(CSF)/BBB value/WBCCSF, and between the CCL2 index and ALB(CSF). sVCAM-1(Serum) was positively associated with event-free survival (EFS), and patients with higher levels of ALB(CSF), MMP-9(CSF/Serum), CCL2(CSF/Serum), and sVCAM-1(CSF/Serum) had shorter EFS. MMP-9(CSF), CCL2(CSF) and sVCAM-1(CSF) 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.