Prognostic significance of IL-6 and IL-8 ascites levels in ovarian cancer patients

Abstract

BackgroundThe acellular fraction of epithelial ovarian cancer (EOC) ascites promotes de novo resistance of tumor cells and thus supports the idea that tumor cells may survive in the surrounding protective microenvironment contributing to disease recurrence. Levels of the pro-inflammatory cytokines IL-6 and IL-8 are elevated in EOC ascites suggesting that they could play a role in tumor progression.MethodsWe measured IL-6 and IL-8 levels in the ascites of 39 patients with newly diagnosed EOC. Commercially available enzyme-linked immunosorbent assay (ELISA) was used to determine IL-6 and IL-8 ascites levels. Ascites cytokine levels were correlated with clinicopathological parameters and progression-free survival.ResultsMean ascites levels for IL-6 and IL-8 were 6419 pg/ml (SEM: 1409 pg/ml) and 1408 pg/ml (SEM: 437 pg/ml) respectively. The levels of IL-6 and IL-8 in ascites were significantly lower in patients that have received prior chemotherapy before the surgery (Mann-Whitney U test, P = 0.037 for IL-6 and P = 0.008 for IL-8). Univariate analysis revealed that high IL-6 ascites levels (P = 0.021), serum CA125 levels (P = 0.04) and stage IV (P = 0.009) were significantly correlated with shorter progression-free survival. Including these variables in a multivariate analysis revealed that elevated IL-6 levels (P = 0.033) was an independent predictor of shorter progression-free survival.ConclusionElevated IL-6, but not IL-8, ascites level is an independent predictor of shorter progression-free survival.

Overexpression of Semaphorin4D Indicates Poor Prognosis and Prompts Monocyte Differentiation toward M2 Macrophages in Epithelial Ovarian Cancer

“…Ishida et al reported that soluble human SEMA4D could induce the production of pro-inflammatory cytokines by MO/MAs, including IL-6 and IL-8 (Ishida et al, 2003). Significantly, previous study proved elevated IL-6 in ascites suggested a shorter progression-free survival (PFS) of EOC patients (Lane et al, 2011) and EOC cell invasion and migration were accelerated due to IL-8 over-expression . Delaire S et al had also reported that human soluble SEMA4D inhibits both the spontaneous and induced migration of MO/ MAs in tumor microenvironments (Delaire et al, 2001).…”

Revisiting the Complexity of the Ovarian Cancer Microenvironment—Clinical Implications for Treatment Strategies

“…11,12). To evaluate the prognostic significance of IL-6 and IL-8 levels in ascites, Lane and colleagues correlated levels to a number of clinical measures, including progression-free survival (12). Using multivariate analyses, the authors concluded that IL-6 could serve as a predictor of shorter progression-free survival ( (14).…”

“…11,12). To evaluate the prognostic significance of IL-6 and IL-8 levels in ascites, Lane and colleagues correlated levels to a number of clinical measures, including progression-free survival (12).…”

Inflammation and ovarian cancer

“…In fact, IL-6 has an important role, precisely through tumour angiogenesis, in promoting the development of ascites as well as the spread of ovarian cancer thus leading to fast progression and short survival. (Lane, 2011;Lo, 2011). The high levels of IL-6 enhance the immune suppressive status of the tumour microenvironment by inhibiting IL-2 synthesis, T cell activation and proliferation, and promoting lymphocytes apoptosis (Macciò, 1998;Mantovani, 1999a).…”