title: Evaluation of serum procathepsin B, cystatin B and cystatin C as possible biomarkers of ovarian cancer.
abstract: OBJECTIVE
  To evaluate procathepsin B, as well as endogenous inhibitors of cysteine proteases (cystatin B and cystatin C) in biological fluids as possible biomarkers of ovarian cancer. To observe levels of serum procathepsin B in different age groups.
  
  
  METHODS
  The sample (N=27) of women with gynaecological tumours included 18 patients with ovarian cancer (n=18) and 9 patients with benign ovarian tumours (n=9); 72 healthy women were in the control group. All patients were treated in Novosibirsk Regional Oncological Center, Russia. Serum samples of healthy women (n=40) aged 18-70 years were used as controls for common biomarker of ovarian cancer CA-125. In the Procathepsin B study, serum samples of healthy women (n=32) aged 18-40 years (n=14), 41-55 years (n=10) and 56-80 (n=8) years were used as controls.
  
  
  METHODS
  Common biomarker of ovarian cancer, CA-125, was assayed by using a commercial kit (Vector, Koltsovo, Novosibirsk Region, Russia). Procathepsin B was measured by means of a commercial kit for human procathepsin B (R&D, USA); cystatin C was measured by commercial ELISA kits for human (BioVendor, Czechia); cystatin B was measured by ELISA kits for human (USCN Life Science Inc., Wuhan, China). Statistical analysis was performed by one-way ANOVA (Statistica 10 Program).
  
  
  RESULTS
  In the control group, serum procathepsin B concentration did not reveal age dependency. In the ovarian cancer group, both levels of serum procathepsin B and standard biomarker CA-125 increased significantly (both p<0.001) compared with the control group. In the benign ovarian tumour group, serum procathepsin B (p<0.001) and CA-125 (p=0.004) increased about 2.5- and 8-fold compared to the control group. Serum cystatin B level increased up to 1.7-fold in the ovarian cancer group compared to the control group. The increase of serum CA-125 was about 3.5-fold higher (p=0.017) and procathepsin B was 1.8-fold higher (p<0.05) in the ovarian cancer group compared to the benign tumour group. Cystatin B in ascites fluid increased equally in both ovarian cancer (p<0.001) and benign ovarian tumours group (p<0.05). Cystatin C concentration in ascites fluid increased only in patients with ovarian cancer (p<0.05) and did not change in the benign tumours group. Large increases of procathepsin B level (about 13-fold, p<0.001) and to a lesser degree of cystatin C (1.8-fold, p<0.05) and cystatin B levels (1.4 fold, p<0.001) were revealed in ascites fluids of patients with ovarian cancer compared to the control serum. The significant difference in serum procathepsin B levels was noted between the ovarian cancer and benign tumour groups (p<0.05), which could be used in differential diagnostics between malignant and benign gynaecological tumours.
  
  
  CONCLUSIONS
  Serum procathepsin B demonstrated significant promise as a new biomarker of ovarian cancer.
authors.affiliation: Institute of Physiology SB RAMS, Novosibirsk, Russia.
authors.forename: Elena A
authors.initials: EA
authors.lastname: Gashenko
authors.forename: Valentina A
authors.initials: VA
authors.lastname: Lebedeva
authors.forename: Ivan V
authors.initials: IV
authors.lastname: Brak
authors.forename: Elena A
authors.initials: EA
authors.lastname: Tsykalenko
authors.forename: Galina V
authors.initials: GV
authors.lastname: Vinokurova
authors.forename: Tatyana A
authors.initials: TA
authors.lastname: Korolenko
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D015415:Biomarkers / Q000097:blood; D018394:CA-125 Antigen / Q000097:blood; D016022:Case-Control Studies; D002401:Cathepsin B / Q000097:blood*; D055313:Cystatin B / Q000097:blood*; D055316:Cystatin C / Q000097:blood*; D004792:Enzyme Precursors / Q000097:blood*; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000097:blood* / Q000175:diagnosis; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018394:CA-125 Antigen; D055316:Cystatin C; D004792:Enzyme Precursors; D055313:Cystatin B; C057832:procathepsin B; D002401:Cathepsin B
keywords: biomarkers; cystatin B; cystatin C; ovarian cancer; procathepsin B