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Differential Scanning Calorimetry of Gliomas: A New Tool in Brain Cancer Diagnostics?

Chagovetz, Alexis A. BS*,‡; Quinn, Colette PhD*,¶; Damarse, Neil PhD; Hansen, Lee D. PhD§; Chagovetz, Alexander M. PhD; Jensen, Randy L. MD, PhD

Neurosurgery:
doi: 10.1227/01.neu.0000430296.23799.cd
Research-Human-Clinical Studies
Abstract

BACKGROUND: Thermal stability signatures of complex molecular interactions in biological fluids can be measured using differential scanning calorimetry (DSC). Evaluating the thermal stability of plasma proteomes offers a method of producing a disease-specific “signature” (thermogram) in neoplastic and autoimmune diseases.

OBJECTIVE: The authors describe the use of DSC with human brain tumor tissue to create unique thermograms for correlation with histological tumor classification.

METHODS: Primary brain tumors were classified according to the World Health Organization classification. Tumor samples were digested and assayed by a DSC calorimeter. Experimental thermograms were background subtracted and normalized to the total area of transitions to exclude concentration effects. The resulting thermograms were analyzed by applying 2-state, scaled, Gaussian distributions.

RESULTS: Differences in glioma-specific signatures are described by using calculated parameters at transitions that are characterized, in the equilibrium approximation, by a melting temperature (Tm), an apparent enthalpy change (ΔH), and a scaling factor related to the relative abundance of the materials denatured in the transition (Aw). Thermogram signatures of glioblastoma multiforme and low-grade astrocytomas were differentiated by calculated values of Aw3 and Tm4, those of glioblastoma multiforme and oligodendrogliomas were differentiated by Aw2, ΔH2, ΔH4, and Tm4, and those of low-grade astrocytomas and oligodendroglioma were differentiated by Aw4.

CONCLUSION: Our preliminary results suggest that solid brain tumors exhibit specific thermogram profiles that are distinguishable among glioma grades. We anticipate that our results will form the conceptual base of a novel diagnostic assay based on tissue thermograms as a complement to currently used histological analysis.

ABBREVIATIONS: ANOVA, analysis of variance

DSC, differential scanning calorimetry

GBM, glioblastoma multiforme

PBS, phosphate-buffered saline

WHO, World Health Organization

Author Information

Department of Neurosurgery, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah;

TA Instruments, Inc, Lindon, Utah;

§Department of Chemistry, Brigham Young University, Provo, Utah

Correspondence: Randy L. Jensen, MD, PhD, Department of Neurosurgery, University of Utah, 175 N. Medical Drive East, Salt Lake City, UT 84132. E-mail: randy.jensen@hsc.utah.edu

* These authors contributed equally to this work.

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Received July 9, 2012

Accepted March 25, 2013

Copyright © by the Congress of Neurological Surgeons