RESUMO
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.
RESUMO
BACKGROUND: The most important prognostic factor in the ovarian cancer is optimal cytoreduction. The neoadjuvant chemotherapy, an only optional method of treatment in this case and is still the subject of debate. The object of this study was to evaluate the usefulness of markers: CA 125, HE4, YKL-40 and bcl-2 as well as cathepsin L in predicting optimal cytoreduction and response to chemotherapy. METHODS: Sera were secured preoperatively. The division into groups was performed retrospectively depending on the method of treatment (surgery vs neoadjuvant chemotherapy) as well as on response to chemotherapy (sensitive vs resistant vs refractory). Comparisons were made between groups, and the diagnostic usefulness of tested proteins was examined. RESULTS: We found that statistically significant differences between primary operated patients and patients undergoing neoadjuvant chemotherapy were applicable only to the tumour markers (CA125 1206.79 vs 2432.38, p=0.000191; HE4 78.87 vs 602.45, p=0.000004; YKL-40 108.13 vs 203.96, p=0.003991). Cathepsin-L and Bcl-2 were statistically insignificant. The cut-off point values were determined for the CA 125 (345 mIU/ml), HE4 (218.43 pmol/L) and YKL-40 (140.9 ng/ml). The sensitivity, specificity, PPV and NPV were as follows: CA125 (83.3%; 75%; 80.6%; 78.3%), HE4 (86.6%; 91.3%; 92.9%; 84%) and YKL-40 (75%; 83.3%; 84%; 74.1%). CONCLUSION: Among the tested proteins the HE4 marker appears to be helpful in forecasting of optimal cytoreduction and possibly also of the prediction of response to platinum analogues used in first-line treatment of ovarian cancer.