胃癌患者血红蛋白的表面增强拉曼光谱分析

胃癌患者能够得到早期诊断对其治疗具有十分重要的意义，疾病状态下的血红蛋白拉曼光谱检测在血液代用品的高铁血红蛋白含量检测中以及血氧饱和定量测定中占很大优势。本实验采用微波加热法制备银胶体粒子，依次对20例胃癌患者和11例健康人的血红蛋白进行表面增强拉曼光谱分析。采用SERS谱峰归属分析结果显示胃癌患者血红蛋白中的酪氨酸、苯丙氨酸和吡咯环的含量均低于正常人。本文还讨论了血红素的分子结构，在血红蛋白和氧气结合的前后，Fe2+分别处于高低自旋态，离子半径也随着与氧结合缩小了0.075 nm从而滑落入卟啉环平面中央的孔隙之中。这种空间的拉伸变化会牵动与铁相连的F8His，使得珠蛋白中两股螺旋之间空隙缩小，导致将HC2酪氨酸排挤出空隙。利用这一机理，对血红蛋白1 560 cm-1的吸收峰进行研究，证实了胃癌患者酪氨酸含量确实低于正常人。为了能得到更加明显的诊断区分，利用降维的思想，采用主成分分析(PCA)的方法对所有的拉曼光谱进行多元统计分析，得出三维的诊断散点图。为了更加精确的得出诊断准确率，用判别分析得出诊断的灵敏度和特异性分别为90.0%和90.9%，总判别正确率为90.3%。此项研究表明：对氧合血红蛋白的表面增强拉曼光谱诊断分析有希望成为一项新型的胃癌诊断技术应用于医学领域。

Research on Early Diagnosis of Gastric Cancer by the Surface Enhanced Raman Spectroscopy of Human Hemoglobin

Early diagnosis have great positive effect on the treatment of gastric cancer patients. Raman spectroscopy can provide a useful monitor for hemoglobin dynamics. Besides, Raman spectroscopy has notable advantages in the fields of abnormal hemoglobin diagnosis, hemoglobin oxygen saturation deter mination and blood methemoglobin analysis. In this paper, novel silver colloid was synthesized by microwave heated method. The surface enhanced Raman spectrums of hemoglobin from 11 normal persons and 20 gastric cancer patients are measured and analyzed in order to obtain spectrums which are high repeatability and characteristic peaks protruding. By analyzing the assignations of the SERS bands, it found that the content of asparagine, tyrosine and phenylalanine in the hemoglobin are significantly lower than healthy people. Discussing the structure of hemoglobin, when hemoglobin combines with oxygen, Fe2+is in a low spin state, ionic radius shrinks and moves 0.075 nm and fall into the pore in the middle of the heme porphyrin ring plane. This spatial variation affects F8His connected with the iron, will narrow the gap between the globin in the two strands of the helix, as a result，HC2 tyrosine pushed out of the void. Using this mechanism，the absorption peak of 1 560 cm-1 confirmed that the tyrosine content in patients with gastric cancer was lower than that of normal people. Principal component analysis(PCA) is employed to get a three-dimensional scatter plot of PC scores for the health and cancer groups, and it can be learned that they are distributed in separate areas. By using the method of discri minate analysis, it is found that the diagnostic algorithm separates the two groups with sensitivity of 90.0% and diagnostic specificity of 90.9%, the overall diagnostic accuracy was 90.3%.The results from this exploratory study demonstrate that, SERS detection of oxyhemoglobin combined with multivariate analysis would be an effective method for early diagnosis of gastric cancer.