Ghimire Hemendra, Garlapati Chakravarthy, Janssen Emiel A M, Krishnamurti Uma, Qin Gengsheng, Aneja Ritu, Perera A G Unil
Department of Physics and Astronomy, Georgia State University, Atlanta, GA 30303, USA.
Department of Biology, Georgia State University, Atlanta, GA 30303, USA.
Cancers (Basel). 2020 Jun 27;12(7):1708. doi: 10.3390/cancers12071708.
Protein structural alterations, including misfolding and aggregation, are a hallmark of several diseases, including cancer. However, the possible clinical application of protein conformational analysis using infrared spectroscopy to detect cancer-associated structural changes in proteins has not been established yet. The present study investigates the applicability of Fourier transform infrared spectroscopy in distinguishing the sera of healthy individuals and breast cancer patients. The cancer-associated alterations in the protein structure were analyzed by fitting the amide I (1600-1700 cm) band of experimental curves, as well as by comparing the ratio of the absorbance values at the amide II and amide III bands, assigning those as the infrared spectral signatures. The snapshot of the breast cancer-associated alteration in circulating DNA and RNA was also evaluated by extending the spectral fitting protocol to the complex region of carbohydrates and nucleic acids, 1140-1000 cm. The sensitivity and specificity of these signatures, representing the ratio of the α-helix and β-pleated sheet in proteins, were both 90%. Likewise, the ratio of amides II and amide III (I/I) had a sensitivity and specificity of 100% and 80%, respectively. Thus, infrared spectroscopy can serve as a powerful tool to understand the protein structural alterations besides distinguishing breast cancer and healthy serum samples.
蛋白质结构改变，包括错误折叠和聚集，是包括癌症在内的多种疾病的标志。然而，利用红外光谱进行蛋白质构象分析以检测与癌症相关的蛋白质结构变化的潜在临床应用尚未确立。本研究调查了傅里叶变换红外光谱在区分健康个体和乳腺癌患者血清方面的适用性。通过拟合实验曲线的酰胺I（1600 - 1700 cm）波段，以及比较酰胺II和酰胺III波段的吸光度值之比来分析蛋白质结构中与癌症相关的变化，并将这些比值作为红外光谱特征。通过将光谱拟合方案扩展到碳水化合物和核酸的复杂区域（1140 - 1000 cm），还评估了循环DNA和RNA中与乳腺癌相关变化的概况。这些代表蛋白质中α - 螺旋和β - 折叠片层比例的特征的灵敏度和特异性均为90%。同样，酰胺II与酰胺III的比值（II/III）的灵敏度和特异性分别为100%和80%。因此，红外光谱除了能区分乳腺癌和健康血清样本外，还可作为理解蛋白质结构改变的有力工具。
