A proteomic strategy to identify novel serum biomarkers for liver cirrhosis and hepatocellular cancer in individuals with fatty liver disease.
A proteomic strategy to identify novel serum biomarkers for liver cirrhosis and hepatocellular cancer in individuals with fatty liver disease.
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DOI：
10.1186/1471-2407-9-271
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发表时间：
2009-08-05
期刊：
影响因子：
3.8
通讯作者：
Reeves HL
中科院分区：
文献类型：
--
作者：
Gray J;Chattopadhyay D;Beale GS;Patman GL;Miele L;King BP;Stewart S;Hudson M;Day CP;Manas DM;Reeves HL
非酒精性脂肪肝（NAFLD）在西方社会的患病率超过20%。受影响的个体有发生肝硬化和肝细胞癌（HCC）的风险。目前还没有成本效益的人口为基础的手段来确定肝癌的个人，即使有，我们的能力进行肝癌监测的风险组是不够的。我们已经进行了一项试点蛋白质组学研究，以评估这作为血清生物标志物检测的策略。对来自3组患者的免疫耗竭血清进行2D凝胶电泳，即患有（1）炎前NAFLD（2）炎性NAFLD和（3）炎性NAFLD与共存的HCC的那些。区分这三个组中至少一个的五个点通过质谱表征。优化了ELISA测定，并对45例脂肪性肝炎相关肝硬化和HCC患者的血清进行了横断面研究，并与77例组织学分期的脂肪性肝炎患者进行了比较。其中4个斑点是载脂蛋白同种型，其模式能够区分三组。第5个斑点见于肝硬化患者血清，在肝细胞癌患者血清中更为明显，被鉴定为CD 5抗原样（CD 5L）。通过ELISA测定，虽然CD 5L在许多患有HCC的患者中显著升高，但其通过AUC ROC分析确定的区分非癌症与癌症个体的总体能力较差。然而，血清CD 5L显着增加，独立于年龄，性别，和坏死性炎症的存在，在血清中的个体与NAFLD肝硬化相对于那些与肝硬化前疾病。这种新的蛋白质组学策略已经确定了许多候选生物标志物，这些生物标志物可能有助于慢性肝病和/或HCC患者的监测和诊断。
Non-alcoholic fatty liver disease (NAFLD) has a prevalence of over 20% in Western societies. Affected individuals are at risk of developing both cirrhosis and hepatocellular cancer (HCC). Presently there is no cost effective population based means of identifying cirrhotic individuals and even if there were, our ability to perform HCC surveillance in the at risk group is inadequate. We have performed a pilot proteomic study to assess this as a strategy for serum biomarker detection. 2D Gel electrophoresis was performed on immune depleted sera from 3 groups of patients, namely those with (1) pre-cirrhotic NAFLD (2) cirrhotic NAFLD and (3) cirrhotic NAFLD with co-existing HCC. Five spots differentiating at least one of these three groups were characterised by mass spectroscopy. An ELISA assay was optimised and a cross sectional study assessing one of these serum spots was performed on serum from 45 patients with steatohepatitis related cirrhosis and HCC and compared to 77 patients with histologically staged steatohepatitis. Four of the spots identified were apolipoprotein isoforms, the pattern of which was able to differentiate the three groups. The 5th spot, seen in the serum of cirrhotic individuals and more markedly in those with HCC, was identified as CD5 antigen like (CD5L). By ELISA assay, although CD5L was markedly elevated in a number of cirrhotic individuals with HCC, its overall ability to distinguish non-cancer from cancer individuals as determined by AUC ROC analysis was poor. However, serum CD5L was dramatically increased, independently of age, sex, and the presence of necroinflammation, in the serum of individuals with NAFLD cirrhosis relative to those with pre-cirrhotic disease. This novel proteomic strategy has identified a number of candidate biomarkers which may have benefit in the surveillance and diagnosis of individuals with chronic liver disease and/or HCC.
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