title: Significance of circulating matrix metalloproteinase-9 to tissue inhibitor of metalloproteinases-2 ratio as a predictor of disease progression in patients with metastatic renal cell carcinoma receiving sunitinib.
abstract: OBJECTIVE
  To assess the significance of circulating matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) as predictors of disease progression in patients with metastatic renal cell carcinoma (mRCC) receiving sunitinib.
  
  
  METHODS
  Circulating levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 in sera from 52 patients with mRCC treated with sunitinib were measured at the baseline and on the first day of each treatment cycle until progression using enzyme-linked immunosorbent assays.
  
  
  RESULTS
  The baseline level of MMP-9 in nonresponders to sunitinib was significantly higher than that in responders, whereas the baseline level of TIMP-2 in nonresponders was significantly lower than that in responders. However, there were no significant differences in the serum levels of MMP-2 and TIMP-1 between responders and nonresponders. The serum MMP-9/TIMP-2 ratio at the baseline in nonresponders was also significantly higher than that in responders. Univariate analysis showed that the MMP-9/TIMP-2 ratio, but not MMP-9 and TIMP-2 levels, was significantly correlated with progression-free survival, and the MMP-9/TIMP-2 ratio, in addition to the Memorial Sloan-Kettering Cancer Center classification and C-reactive protein level, appeared to be independently associated with progression-free survival on multivariate analysis. Furthermore, despite the lack of significant differences in the serum levels of MMP-9 and TIMP-2 between the baseline and the time of progression, the MMP-9/TIMP-2 ratio at the time of progression was significantly elevated compared with the baseline ratio.
  
  
  CONCLUSIONS
  An imbalance between the serum MMP-9 and TIMP-2 levels could be a novel biomarker to predict disease progression in patients with mRCC under treatment with sunitinib.
authors.affiliation: Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan. Electronic address: hideakimiyake@hotmail.com.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Miyake
authors.affiliation: Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Masatomo
authors.initials: M
authors.lastname: Nishikawa
authors.affiliation: Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Hiromoto
authors.initials: H
authors.lastname: Tei
authors.affiliation: Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Furukawa
authors.affiliation: Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Harada
authors.affiliation: Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Fujisawa
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000188:drug therapy*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000097:blood / Q000188:drug therapy*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011758:Pyrroles / Q000627:therapeutic use*; D012189:Retrospective Studies; D000077210:Sunitinib; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D007211:Indoles; D011758:Pyrroles; C560823:TIMP2 protein, human; D019716:Tissue Inhibitor of Metalloproteinase-2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D000077210:Sunitinib
keywords: Matrix metalloproteinase; Renal cell carcinoma; Resistance; Sunitinib; Tissue inhibitor of metalloproteinases