A91

Background

The research for procathepsin B and endogenous inhibitors of cysteine proteases in tumor markers of human reproductive system is important for early diagnostics of cancer. Preform of cathepsin B and cystatins B and C also are universally involved into development of different tumors. Tumor cells as well as tumor-associated macrophages have been shown to secrete active forms of proteases and their inhibitors; however, their roles, especially those of proenzymes as markers of malignancy, are still under investigation.

Aim

to evaluate procathepsin B and endogenous inhibitors of cysteine proteases cystatins B and C in tumors of reproductive system.

Materials and methods

Serum and ascites fluid of 38 patients with ovarian cancer (among them 15 patients after treatment) and benign ovarian tumors (n = 9), endometrial cancer (n = 31, before treatment 14), mammalian cancer (n = 29, before treatment 18) of stages II–IV for all groups, from Department of Gynecology of Regional Oncology Center, Novosibirsk, were under investigation. Serum of practically healthy women aged 18–80 (n = 82) from Regional Diagnostic Center, Novosibirsk, was used as a control group. Serum of women with tumors of the reproductive system and ascites fluids of women with ovarian tumors (aged 18–80 years), before operation were used for assay of procathepsin B, cysteine protease inhibitors cystatins B and C. Serum procathepsin B concentration was measured by ELISA commercial kit for human (R&D) USA; cystatin C using BioVendor commercial kits (Czechia), cystatin B – with help of ELISA kits for human (USCN Life Science Inc., Wuhan, China). Common biomarker of ovarian cancer, CA-125, was assayed by using a commercial kit (Vector, Koltsovo, Novosibirsk Region, Russia). Statistical analysis performed by one a way ANOVA Statistic 12, program with help of Kruskall–Wallis test and the Mann–Whitney U test used to assess differences in procathepsin B or cystatins B and C levels between patient groups. Statistical analysis was performed with the soft package Statistics 12, with the level of significance being set at <0.05.

Results

In serum of patients with endometrial cancer, ovarian cancer, mammalian cancer – significant increases in serum procathepsin B (p < 0.001), cystatin B (p < 0.05) and CA-125 (p < 0.001) were noted. However, in patients with benign tumor increased serum common tumor marker CA-125 (p = 0.005 vs. healthy controls) was shown without any changes in serum level of procathepsin B, cystatins B and C. Concentrations procathepsin B and Cystatin B in serum and ascites of patients with ovarian tumor was used to assess differences in procathepsin B or cystatins B and C levels between groups. Serum procathepsin B(p < 0.05) and in ascites fluid of patients with ovarian cancer (p < 0.001) was shown to significant increase in ovarian cancer group vs. benign ovarian tumors group. The concentration of CA-125 in ascites of patients with ovarian cancer (p < 0.000) and benign ovarian tumors (p < 0.05) was high, but has not differences between them (p > 0.1).

Conclusion

One can conclude that serum procathepsin B and endogenous inhibitors of cysteine proteases cystatin B are prospective tumor biomarkers in reproductive system tumors. Procathepsin B and cystatin B seem to be important in differential diagnosis of ovarian cancer and benign ovarian tumors. Procathepsin B and cystatin B are involved in breast and endometrial cancer that warrants further investigation of their role in cancer.