Background: Ovarian cancer (OC) is the most common cause of death among gynecologic cancers. A key reason for the high lethality of OC is that early detection of OC is uncommon, and the majority of OC patients have advanced stage disease at diagnosis. Current non-invasive tests do not adequately distinguish benign from malignant adnexal masses. Diagnostic tests that reliably distinguish early stage OC from benign conditions may lead to earlier diagnosis of OC and improved survival.
Methods: We designed a cohort study of plasma biomarkers in ovarian cancer patients. Specimens were analyzed from 100 patients with advanced OC (AJCC Stage III and IV), 50 patients with early stage OC (Stage I and II), and 50 patients with benign surgical conditions from the Mayo Ovarian SPORE Biospecimens Core. Presurgical plasma samples were assayed for multiple toll-like receptor agonists, cytokines, and vascular growth factors by ELISA and electrochemiluminescence. Biomarkers that were reliably detected in plasma were analyzed for association with OC. Differences in plasma biomarker levels between benign, early, and advanced OC patient groups were assessed using plate-adjusted logistic regression models.
Results: Out of 23 biomarkers tested, 7 were excluded due to unreliable plasma detection. Of the remaining 16 biomarkers, 6_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 OC (all p<0.005), and one_IL-6_was associated with early stage OC (p < 0.0001). Heat shock protein 90kDa beta member 1 (HSP90B1, gp96) was associated with OC and early stage OC with borderline statistical significance (p = 0.039 and p = 0.026, respectively). However, when adjusted for cancer antigen 125 (CA-125), only HSP90B1 independently predicted OC (p = 0.008), as well as early stage OC (p = 0.014).
Conclusions: The plasma cytokines IFNγ, IL-6, IL-8, IL-10, TNFα, and PlGF are associated with OC. However, after adjusting for CA-125, only HSP90B1 independently predicts OC, including early stage OC. These data warrant further investigation to determine whether measuring plasma HSP90B1 can aid in patient evaluation.
Citation Format: Matthew S. Block, Matthew J. Maurer, Krista Goergen, Kimberly R. Kalli, Courtney L. Erskine, Marshall D. Behrens, Keith L. Knutson. Plasma heat shock protein 90kDa beta member 1 levels predict both early stage and advanced stage ovarian cancer independently from cancer antigen 125 in patients with an indeterminate adnexal mass. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1873. doi:10.1158/1538-7445.AM2014-1873