Cytokines as Prognostic Biomarkers of Epithelial Ovarian Cancer (EOC): A Systematic Review and Meta-Analysis

Objectives: The value of cytokines as epithelial ovarian cancer (EOC) prognostic factors has been widely investigated. This study aimed to determine the role of single cytokine as a biomarker prognosis in EOC. Materials and Methods: We conducted a systematic review and meta-analysis of studies reporting cytokine as the prognostic predictor in EOC based on PRISMA guideline. We included English articles investigating associations of preoperative cytokines level in tissue, blood or ascites with overall survival (OS) or disease-free survival (DFS) from PUBMED and EBSCO. Summary hazard ratios (HRs) and confidence intervals (CIs) were calculated. Results: Fifty studies investigating twenty types of cytokines in tumor tissue, serum, and ascites from 5,376 patients were included. Pre-operative high VEGF level was associated with poor OS (HR 2.28, 95%CI 1.28, 3.28]) and DFS (HR 2.13, 95%CI 1.63, 2.78]) in serum and OS (HR 1.80, 95%CI 1.45, 2.23]) in tissue. IL-6 level in blood was associated with DFS (HR 1.60, 95%CI 1.21, 2.11]). There was no single cytokine which investigated by at least 2 studies reporting hazard ratio in ascites, so we did not conduct the meta-analysis. Other cytokines (serum IL-8; ascites fluid IL-8, IL-10, IFN-γ, TNF-α; and ovarian tissue TGF-α, CSF-1, IL-10 ,TGF-β1, IL-17) associated with the poorer prognosis, could not be pooled due to lack of studies. Conclusion: Pre-operative VEGF level in serum and tissue specimen seem to be the potential candidate of an unfavorable prognostic biomarker for EOC. The evidence was lacking to support the other cytokines investigated in blood, tissue and ascites as prognostic biomarkers for EOC.