Relationship between the blood levels of inflammatory cytokines and the number of circulating tumor cells with response to standard chemotherapy in patients with ovarian cancer

Abstract

Introduction. Serum chemokines are inflammatory mediators, which role is shown in the occurrence and progression of a number of malignant tumors. Produced by white blood cells, stem cells, tumor and endothelial cells, chemokines control their movement and positioning. Chronic inflammation underlies the progression of ovarian cancer (OC). This increases the likelihood of chemokines stimulating or blocking tumor progression. The aim of the study was to evaluate the relationship between the blood levels of inflammatory cytokines in blood and the number of circulating tumor cells (CTCs) with the response to standard chemotherapy (CT) in patients with cancer. Material and Methods. In patients with primary OC before and after 2–4 courses of chemotherapy and in patients with benign ovarian tumors (as a control), serum levels of CCL2, CCL3, CCL4, CXCL8 and CX3CL1 were evaluated by multiplex xMAP analysis. The amount of CTCs (population CD45-/ Epcam+/CK+) was determined using a flow cytometer. Patients with ovarian cancer were divided into 3 groups according to the platinum sensitivity criterion of GCJG 4th, and progression-free interval (PFI) was determined. Results. It was found that the levels of CCL2, CCL3, CCL4, CXCL8, and CX3CL1 in case of OC did not significantly differ from that in the control, strongly negatively correlated with age (except for the CCL2 level). CT significantly increased the level of CCL2 in the group of refractory OC; of CCL3 – in the group of sensitive OC, of CCL4 – in the groups of resistant and sensitive OC, and CXCL8 level increased in the groups with resistant and sensitive OC and decreased in the group of refractory OC. The number of CTCs in patients with OC was significantly higher than in the control. After CT, a decrease in the amount of CTCs strongly and significantly correlated with a decrease in the level of CX3CL1 in the groups of refractory and sensitive OC. The maximum PFI occurred with an increase in serum levels of CCL3, CXCL8, a decrease in CCL4 and a constant level of CX3CL1. Conclusion. Thus, no significant differences in the levels of CCL2, CCL3, CCL4, and IL-8 between patients with OC and control groups were found. The levels of chemokines studied and the amount of CTCs differed in the groups divided by the tumor sensitivity to CT. We observed significant correlations between the amount of CTCs and the level of CX3CL1 in the group of platinum-sensitive OC.