Analysis of transition metal content in glioblastoma reveals association between iron and survival.

in Translational oncology by Ganesh Shenoy, Aurosman Sahu, Madison Kuhn, Vladimir Khristov, Madison Heebner, Hannah Wilding, Taylor Clegg, Debarati Bhanja, Quinn Wade, Laura J Liermann, Dongxiang Wang, Nataliya Smith, Gabriela Remite-Berthet, Chachrit Khunsriraksakul, Kondaiah Palsa, Becky Slagle-Webb, Alireza Mansouri, Brad E Zacharia, Elizabeth A Proctor, James R Connor

TLDR

  • A study found that higher plasma iron levels are associated with improved survival in glioblastoma patients, suggesting potential as a prognostic marker.
  • The study also identified associations between iron and immune profiling in glioblastoma patients, but not in healthy individuals.

Abstract

Little is known about the role of transition metals in glioblastoma progression. Here we investigated whether transition metal content is associated with glioblastoma outcomes. Tumor samples were obtained from 37 newly diagnosed patients with glioblastoma, 21 of which had matched plasma. Iron, zinc, manganese, and copper content in those samples was quantified via inductively-coupled mass spectrometry or atomic emission spectrometry, and subsequently analyzed for associations with overall survival. Multiplexed immune profiling was performed to determine whether transition metal content was associated with altered cytokine profiles. Higher plasma iron levels were strongly associated with prolonged survival (Kaplan-Meier analysis: 30.15 months vs. 12.43 months, P = 0.0036; Multivariate Cox regression analysis: HR: 0.79 [0.64 - 0.97], P = 0.03). Zinc, manganese, and copper concentration in plasma or tumor and iron in tumor were not significantly associated with overall survival. Immune profiling of plasma and tumor samples revealed that plasma iron correlated with plasma IFN-β concentration (R = 0.63, P = 0.0057) in patients with glioblastoma. No correlation of plasma iron and IFN-β was observed in age- and sex- matched healthy individuals (R = -0.15, P = 0.153). Plasma transition metal concentration did not correlate with tumor transition metal concentration. Within tumors, manganese and zinc were correlated (R = 0.52, P = 0.0048) as well as copper and zinc (R = 0.36, P = 0.038). Plasma iron is associated with survival in glioblastoma patients and may serve as a prognostic marker. The mechanisms underlying this association require further study.

Overview

  • The study investigated the association between transition metal content and glioblastoma outcomes, specifically overall survival.
  • The study analyzed iron, zinc, manganese, and copper content in tumor and plasma samples from 37 newly diagnosed glioblastoma patients and 21 with matched plasma.
  • The primary objective was to determine whether transition metal content is associated with overall survival and identify potential biomarkers for glioblastoma prognosis.

Comparative Analysis & Findings

  • Higher plasma iron levels were significantly associated with prolonged survival (30.15 months vs. 12.43 months, P = 0.0036).
  • Zinc, manganese, and copper concentration in plasma or tumor and iron in tumor were not significantly associated with overall survival.
  • Plasma iron correlated with plasma IFN-β concentration in glioblastoma patients, but not in age- and sex-matched healthy individuals.

Implications and Future Directions

  • Plasma iron may serve as a prognostic marker for glioblastoma patients, with higher levels associated with improved survival.
  • The mechanisms underlying the association between plasma iron and survival require further study, including investigations into the role of iron in glioblastoma immune profiling.
  • Future studies should explore the potential of transition metals as biomarkers for glioblastoma diagnosis and monitoring.
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