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基于丙型肝炎病毒网络的肝细胞性肝硬化和肝癌分类。

Hepatitis C virus network based classification of hepatocellular cirrhosis and carcinoma.

机构信息

Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China.

出版信息

PLoS One. 2012;7(4):e34460. doi: 10.1371/journal.pone.0034460. Epub 2012 Apr 6.

Abstract

Hepatitis C virus (HCV) is a main risk factor for liver cirrhosis and hepatocellular carcinoma, particularly to those patients with chronic liver disease or injury. The similar etiology leads to a high correlation of the patients suffering from the disease of liver cirrhosis with those suffering from the disease of hepatocellular carcinoma. However, the biological mechanism for the relationship between these two kinds of diseases is not clear. The present study was initiated in an attempt to investigate into the HCV infection protein network, in hopes to find good biomarkers for diagnosing the two diseases as well as gain insights into their progression mechanisms. To realize this, two potential biomarker pools were defined: (i) the target genes of HCV, and (ii) the between genes on the shortest paths among the target genes of HCV. Meanwhile, a predictor was developed for identifying the liver tissue samples among the following three categories: (i) normal, (ii) cirrhosis, and (iii) hepatocellular carcinoma. Interestingly, it was observed that the identification accuracy was higher with the tissue samples defined by extracting the features from the second biomarker pool than that with the samples defined based on the first biomarker pool. The identification accuracy by the jackknife validation for the between-genes approach was 0.960, indicating that the novel approach holds a quite promising potential in helping find effective biomarkers for diagnosing the liver cirrhosis disease and the hepatocellular carcinoma disease. It may also provide useful insights for in-depth study of the biological mechanisms of HCV-induced cirrhosis and hepatocellular carcinoma.

摘要

丙型肝炎病毒(HCV)是肝硬化和肝细胞癌的主要危险因素,尤其是对那些患有慢性肝病或肝损伤的患者。相似的病因导致肝硬化和肝细胞癌患者的相关性很高。然而,这两种疾病之间的关系的生物学机制尚不清楚。本研究旨在探讨 HCV 感染蛋白网络,希望找到诊断这两种疾病的良好生物标志物,并深入了解其进展机制。为此,定义了两个潜在的生物标志物池:(i)HCV 的靶基因,和(ii)HCV 靶基因之间最短路径上的基因。同时,开发了一个预测器来识别以下三类肝组织样本:(i)正常,(ii)肝硬化,和(iii)肝细胞癌。有趣的是,观察到从第二个生物标志物池提取特征定义的组织样本的识别准确性高于基于第一个生物标志物池定义的样本。Jackknife 验证的基因间方法的识别准确率为 0.960,表明该新方法在帮助寻找诊断肝硬化和肝细胞癌的有效生物标志物方面具有相当大的潜力。它还可能为深入研究 HCV 诱导的肝硬化和肝细胞癌的生物学机制提供有用的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8258/3321022/2de969e670dd/pone.0034460.g001.jpg

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