New multi protein patterns differentiate liver fibrosis stages and hepatocellular carcinoma in chronic hepatitis C serum samples

瞄准：识别一多象用为肝纤维变性(F1-F2 ) 的察觉和区别的提高表面的激光 desorption/ionisation time-of-flight 团 spectrometry (SELDI-TOF-MS ) 的单个蛋白质标记一样的浆液蛋白质模式，在有长期的丙肝病毒(HCV ) 的病人的肝肝硬化(F4 ) andhepatocellular 癌(HCC ) 。方法：有 F1/F2 纤维变性的 39 个病人，的 Serumsamples 有 F4 纤维变性的 44 个病人，有我们重新申请到 CM10 数组并且分析了使用 SELDI-TOF ProteinChip 系统的 HCC 的 34 个病人(PBS-IIc；CiphergenBiosystems ) 在阴离子交换分别以后。所有病人 andhistologically 有长期的丙肝证实的纤维变性 stage/HCC。数据被 multivariatestatistical 技术和人工的神经网络为蛋白质模式分析。结果：4 肽 / 蛋白质 multimarkerpanel (7486， 12843， 44293 和 53598 Da ) 正确地在训练样品(AUROC0.943 ) 的 HCV 肝硬化对 HCV-HCC 的二方法比较与 100% 的敏感和 85% 的特性识别了 HCC。为 HCC 的鉴定的敏感和特性为随机的测试样品是 68% 和 80% 。肝脏硬化症的病人能被歧视有多使用 5peptide/protein 的 F1 或 F2 纤维变性的病人标记模式( 2873 ， 6646 ， 7775 ， 10525 和 67867 Da )与100%和在训练样品( AUROC 0.976 )的85%的敏感和敏感和特性of80%的特性并且67%为随机的测试样品。有 APRI 分数 andalfa-fetopotein (法新社) 的简历标记分类器的联合改进了诊断表演。为肝纤维变性的 6646 Da 标记蛋白质作为 apolipoprotein C-I 被识别。结论：与蛋白质模式分析相结合的 SELDI-TOF-MS 技术与长期的丙肝在病人为肝肝硬化 andhepatocellular 癌的鉴定似乎是一条珍贵途径。最可能，不同浆液标记的联合将帮助以后识别肝肝硬化和早阶段的 hepatocellularcarcinomas。

AIM： To identify a multi serum protein pattern as well as single protein markers using surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry （SELDI-TOF-MS） for detection and differentiation of liver fibrosis （F1-F2）, liver cirrhosis （F4） and hepatocellular carcinoma （HCC） in patients with chronic hepatitis C virus （HCV）. METHODS： Serum samples of 39 patients with F1/F2 fibrosis, 44 patients with F4 fibrosis, 34 patients with HCC were applied to CM10 arrays and analyzed using the SELDI-TOF ProteinChip System （PBS-Ⅱc; Ciphergen Biosystems） after anion-exchange fractionation. All patients had chronic hepatitis C and histologically confirmed fibrosis stage/HCC. Data were analyzed for protein patterns by multivariate statistical techniques and artificial neural networks. RESULTS： A 4 peptide/protein multimarker panel （7486, 12843, 44293 and 53598 Da） correctly identified HCCs with a sensitivity of 100% and specificity of 85% in a two way-comparison of HCV-cirrhosis versus HCV-HCC training samples （AUROC 0.943）. Sensitivity and specificity for identification of HCC were 68% and 80% for random test samples. Cirrhotic patients could be discriminated against patients with F1 or F2 fibrosis using a 5 peptide/protein multimarker pattern （2873, 6646, 7775, 10525 and 67867 Da） with a specificity of 100% and a sensitivity of 85% in training samples （AUROC 0.976） and a sensitivity and specificity of 80% and 67% for random test samples. Combination of the biomarker classifiers with APR/score and alfa-fetopotein （AFP） improved the diagnostic performance. The 6646 Da marker protein for liver fibrosis was identified as apolipoprotein C-I. CONCLUSION： SELDI-TOF-MS technology combined with protein pattern analysis seems a valuable approach for the identification of liver cirrhosis and hepatocellular carcinoma in patients with chronic hepatitis C. Host probably a combination of different serum markers will help to identify liver cirrhosis and early-stage hepatocellular carcinomas in the future.