Evaluation of serum procathepsin B, cystatin B and cystatin C as possible biomarkers of ovarian cancer.

Objectives: 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.

Study Design: 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.

Conclusion: Serum procathepsin B demonstrated significant promise as a new biomarker of ovarian cancer.