‡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.
Neurosurgery. 2013 Aug;73(2):289-95; discussion 295. doi: 10.1227/01.neu.0000430296.23799.cd.
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.
The authors describe the use of DSC with human brain tumor tissue to create unique thermograms for correlation with histological tumor classification.
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.
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.
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.
生物体液中复杂分子相互作用的热稳定性特征可以使用差示扫描量热法(DSC)来测量。评估血浆蛋白质组的热稳定性提供了一种在肿瘤和自身免疫性疾病中产生疾病特异性“特征”(热谱)的方法。
作者描述了使用 DSC 对人脑肿瘤组织进行分析,以创建与组织学肿瘤分类相关的独特热谱。
根据世界卫生组织的分类对原发性脑肿瘤进行分类。对肿瘤样本进行消化并通过 DSC 量热仪进行检测。实验热谱扣除背景并归一化为总转换面积,以排除浓度效应。通过应用 2 态、缩放、高斯分布来分析得到的热谱。
通过使用在平衡近似下由熔融温度(Tm)、表观焓变(ΔH)和与转变中变性材料的相对丰度相关的缩放因子(Aw)来表征的转变的计算参数,描述了神经胶质瘤特异性特征的差异。多形性胶质母细胞瘤和低级别星形细胞瘤的热谱特征通过计算值 Aw3 和 Tm4 来区分,多形性胶质母细胞瘤和少突胶质细胞瘤的热谱特征通过 Aw2、ΔH2、ΔH4 和 Tm4 来区分,低级别星形细胞瘤和少突胶质细胞瘤的热谱特征通过 Aw4 来区分。
我们的初步结果表明,实体脑肿瘤表现出可区分胶质瘤分级的特定热谱特征。我们预计,我们的结果将形成基于组织热谱的新型诊断测定的概念基础,作为对目前使用的组织学分析的补充。