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
‡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: firstname.lastname@example.org
* These authors contributed equally to this work.
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Received July 9, 2012
Accepted March 25, 2013