大肠高分化腺癌与大肠腺瘤的质谱成像

Mass spectrometry imaging for identification of differentially expressed proteins between colorectal adenocarcinoma and colon adenoma

目的:采用质谱成像技术比较大肠高分化腺癌组织与腺瘤组织的蛋白质组表达差异,寻找大肠腺癌相关的蛋白质分子标志物.方法:应用质谱成像技术对人体大肠腺癌组织和大肠腺瘤组织冰冻切片进行质谱扫描,得到蛋白质、多肽的原位分布信息,初步建立了以质谱成像技术寻找大肠高分化腺癌与腺瘤中差异蛋白的方法.质谱成像切片制备:常规10 m冰冻切片,用含0.1%三氟乙酸的50%乙腈水溶液配制成15 g/L的-腈基-4-羟基肉桂酸(-cyano-4-hydroxycinnamic-acid,CHCA)基质均匀喷洒.质谱分析条件:线性正离子模式,激光能量范围30%-50%,照射100次,采样点距200 m.获取到的质谱图采用遗传算法计算峰面积.用峰面积来确定两组之间的差异分子.采用t检验比较两组间峰差异的显著性.结果:与大肠腺瘤比较,大肠高分化腺癌有显著差异蛋白分子共16个,其中上调7个,下调9个.结论:质谱成像技术用于大肠高分化腺癌与大肠腺瘤蛋白质组对照研究能够直观反映出大肠高分化腺癌与大肠腺瘤间的蛋白质分子差异,这些差异分子可能与大肠腺癌的发生、发展相关.

AIM： To identify colorectal adenocarcinoma associated protein molecular markers by com- paring well-differentiated colorectal adenocar- cinoma with adenoma using mass spectrometry imaging technology. METHODS： Frozen tissue sections of human colorectal adenocarcinoma and colon adenoma was scanned by mass spectrometry imaging for polypeptide distribution information in situ. Mass spectrum analysis conditions were linear positive ion mode, laser energy range of 30%-50%, irradiated 100 times, and spot range of 200 I^m. Genetic algorithm was used to calculate peak area. Significantly differential peaks be- tween the two groups were identified by using the t-test. RESULTS： Compared with colorectal adenoma, 16 protein molecules were significantly differen- tially expressed in well-differentiated colorectal adenocarcinoma, including 7 up-regulated and 9 down-regulated. CONCLUSION： Mass spectrometry imaging allows to identify significantly differentially expressed proteins between colorectal adenocar- cinoma and colon adenoma, and these identified molecules may have important roles in the de- velopment of colorectal adenocarcinoma.