Toward the proteomic identification of boomarkers for the prediction of HBV related hepatocellular carcinoma
Toward the proteomic identification of boomarkers for the prediction of HBV related hepatocellular carcinoma
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DOI：
10.1002/jcb.21443
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发表时间：
2008-02-15
影响因子：
4
通讯作者：
Chiu, Jen-Fu
中科院分区：
文献类型：
--
作者：
He, Qing-Yu;Zhu, Rui;Chiu, Jen-Fu
早期发现是有效干预肝细胞癌（HCC）的关键步骤，缺乏敏感特异的生物标志物是HCC相关死亡率高的主要原因。本报告描述了一种结合SELDI-ProteinChip、复杂的算法分析、乙腈（ACN）预处理和双向电泳（2DE）-肽质量指纹（PMF）技术的综合策略，以识别用于预测HBV相关HCC的血清学标志物。应用SELDI-ProteinChip系统对50例HBV相关性肝癌、45例HBV感染者和30例正常人血清标本进行蛋白质组学分析，并对不同蛋白质峰进行逐步统计分析。从统计算法中筛选出分别位于5890、11615和11724 Da的三个最具鉴别力的峰，并构建基于这三个峰的预测模型，并使用新入组的血清样本进行检测。应用2DE技术对经乙腈沉淀处理的血清样品进行分离和比较。经免疫沉淀后的肝癌血清SELDI-TOF谱和Western blot实验证实，PMF鉴定出在12 kDa的2DE区域内明显增强的蛋白质点为血清SAA。鉴于SAA不是特异性生物标志物的事实，正在进一步尝试鉴定另外两个最具区别性的峰，以实现使用预测模型进行HCC监测和预测的可能性。
Early detection is a key step for effective intervention of hepatocellular carcinoma (HCC), the lack of sensitive and specific biomarkers is a major reason for the high rate of HCC-related mortality. This report described an integrated strategy by combining SELDI-ProteinChip, sophisticated algorithm analysis, acetonitrile (ACN) pre-treatment and two-dimensional electrophoresis (2DE)-peptide mass fingerprinting (PMF) techniques to identify serological markers for the prediction of HBV-related HCC. Proteomic profiling of three groups of serum specimens from HBV-related HCC (50 cases), HBV infection (45 cases), and normal subjects (30 cases) was conducted by using SELDI-ProteinChip system and the resulting different protein peaks were Subjected to stepwise statistical analyses. Three most discriminatory peaks at 5890, 11615, and 11724 Da, respectively, were screened out from the statistical algorithm and a predictive model based on the three peaks was constructed and tested using the newly enrolled serum samples. 2DE was applied to separate and compare the serum samples that were pre-treated by ACN precipitation. The protein spots obviously intensified in HCC sera in the 2DE region of 12 kDa were identified by PMF to be serum SAA, which was validated by SELDI-TOF spectra of HCC sera after immunoprecipitation using anti-SAA antibody and by Western blot experiments. Given the fact that SAA is not a specific biomarker, further attempt is being made to identify the other two most discriminatory peaks to realize the possibility of using the predictive model for HCC surveillance and prediction.