Assessment of selected cytokines, proteins, and growth factors in the peritoneal fluid of patients with ovarian cancer and benign gynecological conditions

Anita Monika Chudecka-Głaz,1 Aneta Alicja Cymbaluk-Płoska,1 Janusz Leszek Menkiszak,1 Ewa Pius-Sadowska,2 Bogusław Bronisław Machaliński,2 Agnieszka Sompolska-Rzechuła,3 Izabella Anna Rzepka-Górska1 1Department of Gynecological Surgery and Gynecological Oncology of Adults and Adolescents, Pomeranian Medical University, Szczecin, Poland; 2Department of General Pathology, Pomeranian Medical University, Szczecin, Poland; 3Department of Mathematics Applications in Economy, West Pomeranian University of Technology, Szczecin, Poland Objectives: The ovarian tumor microenvironment, ie, the peritoneal fluid, is an intriguing research subject. The goal of this study was to assess the behavior of selected cytokines and growth factors within the peritoneal fluid in pathologies associated with ascites and to assess the relationship between the levels of these substances and select prognostic factors of ovarian cancer. Methods: A total of 74 patients were enrolled in the study, including 36 patients with ovarian cancer and 38 patients with benign gynecological conditions. Peritoneal fluid collected during surgical procedures was used to assess the levels of interleukin (IL)-6, IL-8, stem cell factor (SCF), dickkopf-1, growth differentiation factor-15 (GDF-15), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), osteoprotegerin (OPG), osteopontin, osteonectin, and human epididymis protein 4. The median levels of these factors were compared between the two groups, and the levels of selected factors were assessed in the ovarian cancer group with regard to the clinical stage of cancer, tumor differentiation, presence of peritoneal spread and positive peritoneal fluid cytology results. The diagnostic value of the analyzed proteins within the peritoneal fluid was also assessed. Results: Differences were observed between the patients with ovarian cancer and the patients with benign gynecological conditions associated with ascites with regard to the levels of IL-6, IL-8, GDF-15, SCF, osteopontin, osteonectin, and OPG. There were no differences in dickkopf-1, TRAIL, and human epididymis protein 4 levels between the two study groups. Cancer stage affected only the mean SCF and OPG levels, with lower SCF values and higher OPG values in advanced cancers compared to less-advanced cancers. Tumor differentiation was associated with significantly lower SCF values in the group of poorly differentiated tumors. A significant reduction in SCF values and a significant increase in OPG and IL-6 values were also observed within cancer cell-positive peritoneal fluid. Peritoneal spread was associated with higher levels of TRAIL, osteonectin, and IL-6 in ovarian cancer patients. Conclusion: On the basis of the conducted studies, it appears that of the studied factors, GDF-15, SCF, and OPG deserve special attention in the context of future research on the tumor microenvironment. With regard to diagnostics, attention should be given primarily to GDF-15, IL-6, and osteonectin. Keywords: ovarian cancer, ascites, cytokines, tumor growth factor, GDF-15, SC