title: Clinical value of combined detection of serum matrix metalloproteinase-9, heparanase, and cathepsin for determining ovarian cancer invasion and metastasis.
abstract: OBJECTIVE
  This study evaluated the clinical value of the combined detection of serum cathepsin L (CL), heparanase (Hpa), and matrix metalloproteinase-9 (MMP-9) for determining the degree of ovarian cancer invasion and metastasis before surgery.
  
  
  METHODS
  Enzyme-linked immunosorbent assays were used to measure the serum content of CL, Hpa, and MMP-9 in 217 patients with untreated ovarian cancer before surgery, 100 patients with benign ovarian tumors, and 101 healthy women as controls. In addition, the degrees of invasion and metastasis were assessed by the 'gold standard' of clinicopathological diagnosis. The associations of the preoperative serum CL, Hpa, and MMP-9 levels with the clinicopathological factors and metastatic status were analyzed. Receiver operating characteristic (ROC) curve analysis was used to evaluate the usefulness of these markers for determining the degree of ovarian cancer invasion before surgery.
  
  
  RESULTS
  The serum CL, Hpa, and MMP-9 levels were significantly higher (p=0.001) in patients with malignant ovarian cancer compared with patients with benign ovarian tumors and healthy controls. The serum CL level was significantly higher in patients with epithelial ovarian carcinoma compared with non-epithelial ovarian carcinoma (p=0.048), whereas the serum levels of Hpa (p=0.109) and MMP-9 (p=0.544) did not differ significantly between these two groups. The serum CL, Hpa, and MMP-9 levels correlated with the degree of differentiation and the FIGO staging (p>0.05). The serum CL (p=0.030) and MMP-9 (p=0.010) levels were significantly associated with peritoneal metastasis, and the serum Hpa level (p=0.042) was associated with distant metastasis. A ROC curve analysis revealed sensitivity of 60.9%, 69.6%, and 72.2%, and specificity of 57.4%, 67.2%, and 68.9% for the preoperative serum levels of CL, Hpa, and MMP-9, respectively, as tumor markers for the degree of extra-pelvic metastasis.
  
  
  CONCLUSIONS
  Elevated serum CL, Hpa, and MMP-9 levels are correlated with malignant invasion and progression in ovarian cancer. The combined detection of serum CL, Hpa, and MMP-9 may be useful for determining the extent of ovarian cancer metastasis before surgery.
authors.affiliation: Department of Gynecologic Oncology, Cancer Hospital, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Hsin-Chih
authors.initials: HC
authors.lastname: Yang
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Yang
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.forename: Su-Mei
authors.initials: SM
authors.lastname: Wang
authors.forename: Zhong-Mian
authors.initials: ZM
authors.lastname: Pan
authors.forename: Bu-Jian
authors.initials: BJ
authors.lastname: Tang
authors.forename: Qingdi Quentin
authors.initials: QQ
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D016022:Case-Control Studies; D056668:Cathepsin L / Q000097:blood*; D005260:Female; D005966:Glucuronidase / Q000097:blood*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010051:Ovarian Neoplasms / Q000097:blood* / Q000201:enzymology / Q000473:pathology*; D011237:Predictive Value of Tests; D012372:ROC Curve; D055815:Young Adult; D000099175:Heparanase
chemical_list: D014408:Biomarkers, Tumor; D056668:Cathepsin L; D005966:Glucuronidase; D020780:Matrix Metalloproteinase 9; D000099175:Heparanase; C534281:CTSL protein, human