采用基质辅助激光解吸电离时间飞行质谱成像技术分析组织切片已在基础与临床医学研究中迅速发展。质谱成像技术通过对冰冻组织切片表面的质谱扫描可以快速直观地得到组织中的分子,如蛋白、多肽等分布信息。采用质谱成像技术对人的非小细胞肺癌组织切片及癌旁组织切片进行研究,对基质覆盖方式和质谱条件进行了优化,初步建立了以质谱成像法寻找非小细胞肺癌中生物标志物的方法。在-20℃制备10μm的冰冻组织切片,用15g·L^-1的α-腈基-4-羟基肉桂酸(含0.1%三氟乙酸)的50%乙腈水溶液,以气流辅助喷洒的方式覆盖在组织切片表面,循环10次,置于干燥器中待干后,用正离子反射式和线性模式分别进行质谱扫描。通过对来自3位患者的10对肺癌/癌旁组织研究,结果表明,癌组织中有m/z3000~3500范围内的特征性簇峰出现。质谱成像技术用于非小细胞肺癌能够直观地在分子水平上反映出癌组织和正常组织间的差异,有望进一步提高肺癌临床诊断的准确度。
Abstract: Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) profiling for tissue section analysis is rapidly developed in foundamental and clinical medical research. Through scanning on the frozen tissue slices, distribution in- formation of molecules such as protein and peptides from a certain tissue were directly ob- tained in little time by profiling MS technology. Based on the profiling MS technology, hu- man being's non-small cell lung cancer (NSCLC) tissue and paracancerous tissue slices were investigated furthermore, matrix application method and mass spectrometry acquisition mode were optimized, a profiling MS method analysis of NSCLC for biomarkers was established afterward. 10 μm frozen tissue slices was prepared at --20 ℃ ,then,15g · L^-1 matrix α-cyano-4-hydroxycinnamic-acid (CHCA) 50% acetonitrile solution containing 0.1% trifluoroacetic acid (TFA) were air-sprayed onto the tissue surface. After ten cycles of coating and drying, tissue slices were placed in a dessicator until completely dried. Both reflector mode and linear mode were employed for mass scan. By investigating 10 couples of NSCLC carcinoma/paracancerous tissue slices from three different patients, it indicates that cluster peaks appears in the m/z ranges from 3 000 to 3 500 is the characteristic of NSCLC. Moreover, the profiling MS technique, which can directly display the differences of carcinoma/ aracancerous tissue at the molecular level, it could be employed to improve the clinical diag- nosis accuracy of NSCLC.