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.

Influences of Gastrointestinal Microbiota Dysbiosis on Serum Proinflammatory Markers in Epithelial Ovarian Cancer Development and Progression

“…Others suggest that local bacterial expansion within the peritoneum may facilitate the formation of metastatic disease [ 57 ]. Furthermore, elevated serum and peritoneal fluid IL-6 concentrations have been reported in women with early- and late-stage EOC compared to those with benign gynecologic conditions [ 58 ]. Moreover, in other cancers, elevated IL-6 levels have been linked to treatment resistance and reduced survival [ 59 ].…”

Autoimmunity, cancer and COVID-19 abnormally activate wound healing pathways: critical role of inflammation

“…serum), making them useful for diagnostic/prognostic purposes to monitor disease progression. This was confirmed on a clinical basis in patients suffering from cutaneous malignant melanoma as well as ovarian, squamous cell, breast and colorectal cancers (Xu et al 2016;Kučera et al 2019;Rezaei et al 2019;Wang et al 2021;Amer et al 2021;Paccagnella et al 2022). For example, in patients with breast cancer, increased levels of IL-4, IL-6, IL-8, IL-10, CCL-2 and IFN-γ are associated with lower survival rates (Paccagnella et al 2022).…”

Two Biosensors for the Determination of Interleukin-6 in Blood Plasma by Array SPRi

“…It also plays a fundamental role in the advanced stage of COVID-19, where it participates in the formation of a dangerous cytokine storm, which is reflected by high IL-6 concentration in blood serum. Elevated IL-6 levels are characteristic of ovarian cancer [ 23 ], gastric cancer [ 24 , 25 ] and esophageal cancer [ 26 ]. IL-6 is a glycoprotein consisting of 212 amino acids with MW in the range 21–30 kDa [ 27 ].…”

“…IL-6 is a glycoprotein consisting of 212 amino acids with MW in the range 21–30 kDa [ 27 ]. The plasma/serum concentration median of healthy controls varies from 1.2 [ 28 ] to 3.96 pg/mL [ 23 ] or 3.2–5.0 pg/mL [ 29 ], while the highest concentration is reported as 19.9 pg/mL. Much higher serous IL-6 concentrations have been reported from patients with ovarian cancer (up to 41.23 pg/mL; [ 23 ]) or acute appendicitis (up to above 1000 pg/mL; [ 29 ]).…”

“…The plasma/serum concentration median of healthy controls varies from 1.2 [ 28 ] to 3.96 pg/mL [ 23 ] or 3.2–5.0 pg/mL [ 29 ], while the highest concentration is reported as 19.9 pg/mL. Much higher serous IL-6 concentrations have been reported from patients with ovarian cancer (up to 41.23 pg/mL; [ 23 ]) or acute appendicitis (up to above 1000 pg/mL; [ 29 ]). IL-6 is determined using the ELISA immunoassay, the Luminex 200 compact analyzer system [ 24 ] or the multiplex analyte profiling technology xMAP [ 30 ].…”