Preliminary use of differential scanning calorimetry of cerebrospinal fluid for the diagnosis of glioblastoma multiforme

Abstract

Thermal stability signatures of complex molecule interaction in biological fluids can be measured using a new approach called differential scanning calorimetry (DSC). The thermal stability of plasma proteome has been described previously as a method of producing a disease-specific "signature," termed thermogram, in several neoplastic and autoimmune diseases. We describe the preliminary use of DSC performed on cerebrospinal fluid (CSF) as a diagnostic tool for the identification of patients with glioblastoma multiforme (GBM). Samples of CSF from nine patients with confirmed GBM were evaluated using DSC, and the thermogram signatures evaluated. These thermograms were compared with thermograms of CSF taken from patients with non-neoplastic conditions such as head trauma, hydrocephalus, or CSF leak. Further analysis was also performed on CSF from patients who had non-GBM neoplastic conditions such as carcinomatosis meningitis or central nervous system lymphoma or leukemia. The DSC thermograms of CSF of the patients with GBM were significantly different when compared with other neoplastic and non-neoplastic cases. The melting temperature of the major transition was shifted by 5°C, which makes it easily distinguishable from control cases. Our results are very preliminary, but it appears that the DSC of CSF has potential utility in diagnostics and monitoring disease progression in GBM patients.

Calorimetric analysis of the plasma proteome: Identification of type 1 diabetes patients with early renal function decline

“…To-date, the thermograms for each disease are markedly different from one other and this leads to our current focus in developing this assay as a clinical diagnostic tool for early disease screening. The general applicability of DSC analysis with potential for clinical diagnostics is further underlined by reports from other investigators indicating promising preliminary results for DSC analysis of a number of diseases [25–30]. Here we report the application of DSC to examine the plasma proteome of selected samples obtained during the 1 st Joslin Study of the Natural History of Microalbuminuria in Type 1 Diabetes [31].…”

Detection of Cervical Cancer Biomarker Patterns in Blood Plasma and Urine by Differential Scanning Calorimetry and Mass Spectrometry

“…Under given solution conditions, a thermogram provides a unique signature for a given protein reflecting specific structural motifs and molecular forces. It has recently been shown that DSC can be applied to the analysis of blood plasma to provide an indication of an individual’s clinical status [15], [16], [17], [18], [19], [20], [21], [22], [23], [24]. The thermogram of plasma from healthy individuals reflected the weighted sum of the denaturation profiles of the most abundant plasma proteins; however, thermograms from individuals with various conditions or diseases were significantly changed [15], [16], [17], [18].…”

Differential Scanning Calorimetry Applied to Cerebrospinal Fluid Analysis in Glioblastoma

“…2,3 In a recent study performed at the University of Utah, DSC was applied to CSF samples obtained from 9 patients with GBM, as well as multiple patients with other tumoral and nontumoral conditions. 4 The thermograms were compared to each other in preliminary fashion to assess for transitions and broadness of peaks. CSF was chosen instead of serum because of being in closer contact to the central nervous system than the serum, potentiating higher sensitivity in the search for GBM-specific proteins.…”