Elevated Interleukin-6 Levels in the Circulation and Peritoneal Fluid of Patients with Ovarian Cancer as a Potential Diagnostic Biomarker: A Systematic Review and Meta-Analysis

Abstract

Ovarian cancer (OC) is one of the most lethal cancers, largely due to a late diagnosis. This study aimed to provide a comprehensive meta-analysis on the diagnostic performance of IL6 in the blood and ascites separately for advanced and early-stage OC. We included 37 studies with 6948 participants detecting serum or plasma IL6. The plasma/serum IL6 mean level in the late-stage OC was 23.88 pg/mL (95% CI: 13.84–41.23), and the early-stage OC was 16.67 pg/mL (95% CI: 510.06–27.61), significantly higher than the healthy controls at 3.96 pg/mL (95% CI: 2.02–7.73), but not significantly higher than those found in the controls with benign growths in the ovary, which was 9.63 pg/mL (95% CI: 4.16–22.26). To evaluate IL6 in ascites as a diagnostic marker, we included 26 studies with 1590 participants. The mean level of ascitic IL6 in the late-stage OC was 3676.93 pg/mL (95% CI: 1891.7–7146.7), and the early-stage OC was 1519.21 pg/mL (95% CI: 604.6–3817.7), significantly higher than the benign controls at 247.33 pg/mL (95% CI: 96.2–636.0). There was no significant correlation between the levels of circulating and ascitic IL6. When pooling all OC stages for analysis, we found that serum/plasma IL6 provided 76.7% sensitivity (95% CI: 0.71–0.92) and 72% specificity (95% CI: 0.64–0.79). Ascitic IL6 provided higher sensitivity at 84% (95% CI: 0.710–0.919) and specificity at 74% (95% CI: 0.646–0.826). This study highlights the utility of ascitic IL6 for early detection of OC.