表面增强的激光解析电离飞行时间质谱技术在肝细胞癌血清学诊断中的应用

Application of surface enhanced laser desorption ionization time-of-flight mass spectrometry technology in the diagnosis of hepatocellular carcinoma

目的:检测HBV感染携带者与肝细胞癌(HCC)患者血清蛋白质的差异性表达,以发现HCC的肿瘤诊断标志物.方法:用表面增强的激光解析电离飞行时间质谱(SELDI-TOF-MS)技术检测27例HCC患者,27例HBV感染携带者,25例健康对照血清中的蛋白质谱,并用Biomarker Patterns System 5．0软件分析,建立诊断模型．结果:检测HCC患者与HBV感染携带者。正常对照与HCC患者,正常对照与HBV感染携带者的差异性蛋白分子,据此构建分类模型,得到的灵敏度和特异度分别为93％,85％; 96％,96％;84％,89％．其中相对分子质量为8141 Da的蛋白峰在HCC组明显高于HBV感染组(p<10-5);相对分子质量为3448 Da的蛋白峰在HCC及HBV感染携带组表达均较正常组显著增高(P<10-5),而在HCC-HBV组无明显差异(P>0．05),提示其可能为HBV感染的一种标志蛋白;相对分子质量为777) Da的蛋白峰在3组中均有差异性表达．结论:SELDI蛋白芯片技术检测血清蛋白质谱法诊断HCC具有较高的灵敏度和特异度,操作简单快捷,临床应用前景广阔,为HCC诊断提供了新的血清学方法．

AIM： To explore tumor markers for the diagnosis of hepatocellular carcinoma （HCC） through detecting the serum protein spectrum differently expressed between hepatitis B virus （HBV） carriers and HCC patients. METHODS： We detected the serum protein spectrum in 27 HCC patients, 27 HBV carriers and 25 healthy controls using surface enhanced laser desorption ionization time-of-flight mass spectrometry （SELDI-TOF-MS） technique, and the diagnosis model was established through analyzing the detected data by biomarker patterns software （BPS） 5.0. RESULTS： The protein peaks, which could discriminate HBV carriers from HCC patients and healthy individuals, as well as healthy individuals from HCC patients, were detected. A diagnosis model based on the detected data was established with the specificity of 93%, 96%, 84%, and sensitivity of 85%, 96%, 89%, respectively. In addition, the 8141-Da protein in HCC patients had a higher expression than that in HBV carriers （P 〈 10^-5）; the expression of 3448-Da protein was higher both in HCC patients and HBV carriers than that in healthy controls （P 〈 10^-5）, but it had no significant difference between HCC patients and HBV carriers （P 〉 0.05）, indicating that 3448-Da protein might be a potential marker for HBV infection; 7771-Da protein was differently expressed between the three groups of patients. CONCLUSION： With a high specificity and sensitivity, the detection of serum protein spectrum can be performed easily and quickly by SELDI-TOF-MS technique, which provides a serological way for the diagnosis of HCC.