Plasma immune analytes in patients with epithelial ovarian cancer

• Plasma IFNγ, IL6, IL8, IL10, TNFα, PlGF and HSP90B1 associate with ovarian cancer.
• IL-6 levels are associated with early stage ovarian cancer.
• HSP90B1 is independently associated with ovarian cancer after adjustment for CA125.

ObjectivesInflammation is a common feature of epithelial ovarian cancer (EOC), and measurement of plasma markers of inflammation might identify candidate markers for use in screening or presurgical evaluation of patients with adnexal masses.MethodsPlasma specimens from cohorts of 100 patients with advanced EOC (AJCC Stage III and IV), 50 patients with early stage EOC (Stage I and II), and 50 patients with benign surgical conditions were assayed for concentrations of multiple cytokines, toll-like receptor agonists, and vascular growth factors via ELISA and electrochemiluminescence. Immune proteins were then analyzed for association with EOC. Differences in plasma protein levels between benign, early, and advanced EOC patient groups were assessed with and without adjustment for plasma cancer antigen 125 (CA-125) levels.ResultsOut of 23 proteins tested, six—including interferon gamma (IFNγ), interleukin 6 (IL-6), IL-8, IL-10, tumor necrosis factor alpha (TNFα), and placental growth factor (PlGF)—were univariately associated with EOC (all p < 0.005), and one—IL-6—was associated with early stage EOC (p < 0.0001). Heat shock protein 90 kDa beta member 1 (HSP90B1, gp96) was associated with EOC and early stage EOC with borderline statistical significance (p = 0.039 and p = 0.026, respectively). However, when adjusted for (CA-125), only HSP90B1 independently predicted EOC (p = 0.008), as well as early stage EOC (p = 0.014).ConclusionsMultiple plasma cytokines, including IFNγ, IL-6, IL-8, IL-10, TNFα, PlGF, and HSP90B1 are associated with EOC. Of these, HSP90B1 is associated with EOC independent from the biomarker CA-125.