EPID-14. ASSOCIATION OF ELEMENTAL IRON WITH GLIOBLASTOMA PATIENT OUTCOMES

Abstract

Abstract Very few studies have examined the role of trace metals, such as iron, in glioblastoma biology and patient outcomes. Here we directly measured iron content in matched glioblastoma tumor and plasma samples using inductively coupled plasma mass spectroscopy (ICP-MS) or inductively coupled plasma atomic emission spectroscopy (ICP-AES), and then studied associations of iron with clinical parameters such as median overall survival (mOS). Elemental iron analysis was performed on a total of 31 glioblastoma samples, 21 of which had matched plasma samples that were analyzed together. Plasma samples from age-matched healthy volunteers were used as a control for comparisons against plasma from glioblastoma patients. Plasma samples from glioblastoma patients had higher levels of iron compared to age-matched healthy control samples (1307.2 ng/mL vs. 575.2 ng/mL, P = .000013). Among glioblastoma patients, higher levels of plasma iron were associated with prolonged survival (mOS: 20.7 months vs. 12.4 months, P = 0.0063). Plasma iron levels, however, were not significantly correlated with tumoral iron levels (R = 0.095, P = 0.70), indicative of regulation between plasma and brain iron. Unsurprisingly, high tumor iron content failed to significantly associate with survival. To gain insights into whether iron may be associated with immune function, we analyzed plasma samples with multiplexed immunoassays. Glioblastoma plasma samples that contained higher levels of iron were associated with increased IFN-β (10.91 pg/mL vs 7.43 pg/mL, P = 0.004) and PDGF-AB/BB (1275.3 pg/mL vs 492.8 pg/mL, P = 0.009), whereas no such association was observed in healthy plasma samples. Our results demonstrate that plasma iron is associated with clinical outcomes and potentially with alterations in IFN-β and/or PDGF-AB/BB signaling in glioblastoma patients. These findings illustrate the importance of iron in glioblastoma biology and demonstrate its potential prognostic value.