title: The prognostic significance of serum and cerebrospinal fluid MMP-9, CCL2 and sVCAM-1 in leukemia CNS metastasis.
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.
authors: Department of Cell Biology and Genetics, Shantou University Medical College, 22 Xinling Road, Shantou, 515041, Guangdong, China.
authors: Meng-Ya
authors: MY
authors: Si
authors: Zhi-Cheng
authors: ZC
authors: Fan
authors: Ya-Zhen
authors: YZ
authors: Li
authors: Xiao-Lan
authors: XL
authors: Chang
authors: Qing-Dong
authors: QD
authors: Xie
authors: Xiao-Yang
authors: XY
authors: Jiao
mesh_terms: D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood / Q000134:cerebrospinal fluid; D016543:Central Nervous System Neoplasms / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000556:secondary; D018932:Chemokine CCL2 / Q000097:blood / Q000134:cerebrospinal fluid; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007938:Leukemia / Q000473:pathology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000134:cerebrospinal fluid; D025341:Principal Component Analysis; D011379:Prognosis; D012372:ROC Curve; D012307:Risk Factors; D012680:Sensitivity and Specificity; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood / Q000134:cerebrospinal fluid; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D019010:Vascular Cell Adhesion Molecule-1; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
references: J Transl Med. 2013 Dec 04;11:298
references: 24304929
references: Biochim Biophys Acta. 2009 Apr;1788(4):872-91
references: 19059202
references: J Clin Immunol. 2006 Jul;26(4):299-307
references: 16652230
references: Blood. 2010 Nov 18;116(20):4251-61
references: 20679526
references: Med Pediatr Oncol. 1986;14(3):191-4
references: 3528788
references: Anticancer Res. 2004 Mar-Apr;24(2C):1243-7
references: 15154654
references: Leuk Res. 2013 Apr;37(4):359-66
references: 23137522
references: J Exp Med. 2001 Mar 19;193(6):713-26
references: 11257138
references: J Neurosci. 2006 Jan 25;26(4):1098-106
references: 16436595
references: Eur J Pediatr. 1997 Jul;156(7):537-40
references: 9243236
references: PLoS One. 2013 Dec 27;8(12):e83887
references: 24386302
references: Blood. 2005 Jan 15;105(2):496-502
references: 15358629
references: Leuk Lymphoma. 2005 Jun;46(6):885-91
references: 16019534
references: Cerebrospinal Fluid Res. 2008 Jan 11;5:1
references: 18186943
references: N Engl J Med. 1996 Jul 4;335(1):43-5
references: 8637541
references: Leuk Res. 2006 Oct;30(10):1259-61
references: 16516290
references: Am J Pathol. 2012 Dec;181(6):1895-9
references: 23063657
references: Tumour Biol. 2014 Jun;35(6):5487-91
references: 24577891
references: Cell. 2011 Oct 14;147(2):275-92
references: 22000009
references: J Neuroimmunol. 2010 Jul 27;224(1-2):80-4
references: 20554025
references: Blood. 2006 Jul 15;108(2):465-72
references: 16556888
references: Neurology. 2000 Apr 25;54(8):1670-6
references: 10762512
references: PLoS One. 2011;6(8):e20599
references: 21857898
references: J Neurooncol. 2011 Sep;104(3):689-96
references: 21359851
references: PLoS One. 2013 Nov 20;8(11):e81007
references: 24278364
references: Cancer. 2010 May 15;116(10):2290-300
references: 20209620
references: J Neurol. 2006 Sep;253(9):1177-84
references: 16998648
references: J Neurochem. 2010 Mar;112(6):1368-85
references: 20028453
references: J Histochem Cytochem. 2008 Feb;56(2):97-109
references: 17938282
references: Eur J Cancer. 2001 Dec;37(18):2392-7
references: 11720833
references: Clin Exp Metastasis. 2014 Feb;31(2):257-67
references: 24306183
references: Oncogene. 2007 Oct 15;26(47):6738-49
references: 17934482
references: Haematologica. 2007 Mar;92(3):332-41
references: 17339182
references: Nat Immunol. 2001 Feb;2(2):108-15
references: 11175802
references: Nature. 2008 Dec 4;456(7222):593-8
references: 19052619
references: N Engl J Med. 1980 Sep 25;303(13):718-22
references: 6157089
references: Nat Rev Immunol. 2003 Jul;3(7):569-81
references: 12876559
references: J Neuroinflammation. 2013 Jul 17;10:86
references: 23866683
references: J Clin Oncol. 2005 Dec 1;23(34):8664-70
references: 16260700
references: J Neurol Sci. 1991 Aug;104(2):215-21
references: 1940975
references: Expert Opin Ther Targets. 2002 Apr;6(2):217-33
references: 12223082
references: J Neurooncol. 2013 May;112(3):329-38
references: 23400753
references: J Neurol Sci. 2006 Sep 25;247(2):202-7
references: 16784758
references: J Neuroimmunol. 2012 Feb 29;243(1-2):81-8
references: 22264765
references: J Peripher Nerv Syst. 2013 Sep;18(3):199-208
references: 24028188
references: J Comp Neurol. 2005 Aug 29;489(3):275-92
references: 16025454
references: Trends Mol Med. 2007 Dec;13(12):535-41
references: 17981506
references: Br J Cancer. 1998 Jun;77(11):1857-63
references: 9667659
references: Eur J Haematol. 1989 Mar;42(3):313-4
references: 2924897
references: Clin Chem. 2008 Dec;54(12):e11-79
references: 19042984
references: Diagn Cytopathol. 1993;9(3):252-8
references: 8519194
references: Neurosurgery. 2009 Oct;65(4):702-8
references: 19834375
references: South Med J. 1976 Aug;69(8):1054-7
references: 822517
references: Clin Exp Immunol. 1998 Nov;114(2):210-4
references: 9822278
references: Leuk Lymphoma. 2012 Oct;53(10):1988-98
references: 22397722
references: N Engl J Med. 1996 Jun 6;334(23):1526-9
references: 8618609
references: J Neuroimmunol. 2008 Jul 31;198(1-2):69-74
references: 18538419
references: Semin Immunol. 1999 Apr;11(2):125-37
references: 10329499
references: J Immunol. 1996 Apr 15;156(8):3017-23
references: 8609424
references: Adv Med Sci. 2006;51:60-5
references: 17357279
references: J Neuropathol Exp Neurol. 2003 Dec;62(12):1254-64
references: 14692701
references: Immunol Lett. 2010 May 4;130(1-2):107-14
references: 20005902
references: Clin Cancer Res. 2000 Mar;6(3):1175-9
references: 10741749
references: Cell. 2000 Oct 27;103(3):481-90
references: 11081634
references: Neuro Oncol. 2014 Apr;16(4):540-51
references: 24311639
references: Cancer. 1998 Feb 15;82(4):733-9
references: 9477107
references: Mol Carcinog. 2013 Jun;52(6):438-45
references: 22241750
references: Stem Cells. 2011 Jan;29(1):32-45
references: 21280157
references: Trends Neurosci. 2001 Dec;24(12):719-25
references: 11718877
references: Eur J Haematol. 1999 Mar;62(3):202-9
references: 10089899
references: Clin Dev Immunol. 2004 Mar;11(1):53-6
references: 15154612
references: J Infect Dis. 2001 Jan 1;183(1):149-53
references: 11106541
references: J Cell Biol. 2000 Nov 13;151(4):879-89
references: 11076971
references: Mol Cell Proteomics. 2012 May;11(5):1-2
references: 22511459
references: Neuroscience. 2009 Jul 7;161(3):806-12
references: 19374937
references: Brain Pathol. 2011 May;21(3):279-97
references: 21029241