Luk John M, Lam Brian Y, Lee Nikki P Y, Ho David W, Sham Pak C, Chen Lei, Peng Jirun, Leng Xisheng, Day Philip J, Fan Sheung-Tat
Department of Surgery and Center for Cancer Research, Faculty of Medicine Building, 9/F, 21 Sassoon Road, University of Hong Kong, Pokfulam, Hong Kong.
Biochem Biophys Res Commun. 2007 Sep 14;361(1):68-73. doi: 10.1016/j.bbrc.2007.06.172. Epub 2007 Jul 10.
Hepatocellular carcinoma (HCC) is a heterogeneous cancer and usually diagnosed at late advanced tumor stages of high lethality. The present study attempted to obtain a proteome-wide analysis of HCC in comparison with adjacent non-tumor liver tissues, in order to facilitate biomarkers' discovery and to investigate the mechanisms of HCC development. A cohort of 66 Chinese patients with HCC was included for proteomic profiling study by two-dimensional gel electrophoresis (2-DE) analysis. Artificial neural network (ANN) and decision tree (CART) data-mining methods were employed to analyze the profiling data and to delineate significant patterns and trends for discriminating HCC from non-malignant liver tissues. Protein markers were identified by tandem MS/MS. A total of 132 proteome datasets were generated by 2-DE expression profiling analysis, and each with 230 consolidated protein expression intensities. Both the data-mining algorithms successfully distinguished the HCC phenotype from other non-malignant liver samples. The detection sensitivity and specificity of ANN were 96.97% and 87.88%, while those of CART were 81.82% and 78.79%, respectively. The three biological classifiers in the CART model were identified as cytochrome b5, heat shock 70 kDa protein 8 isoform 2, and cathepsin B. The 2-DE-based proteomic profiling approach combined with the ANN or CART algorithm yielded satisfactory performance on identifying HCC and revealed potential candidate cancer biomarkers.
肝细胞癌(HCC)是一种异质性癌症,通常在具有高致死率的晚期肿瘤阶段被诊断出来。本研究试图对HCC与相邻非肿瘤肝组织进行全蛋白质组分析,以促进生物标志物的发现并研究HCC的发展机制。纳入了66例中国HCC患者队列,通过二维凝胶电泳(2-DE)分析进行蛋白质组学分析研究。采用人工神经网络(ANN)和决策树(CART)数据挖掘方法分析分析数据,并描绘区分HCC与非恶性肝组织的显著模式和趋势。通过串联质谱/质谱鉴定蛋白质标志物。通过2-DE表达谱分析共生成了132个蛋白质组数据集,每个数据集有230个合并的蛋白质表达强度。两种数据挖掘算法均成功地将HCC表型与其他非恶性肝样本区分开来。ANN的检测灵敏度和特异性分别为96.97%和87.88%,而CART的检测灵敏度和特异性分别为81.82%和78.79%。CART模型中的三个生物学分类器被鉴定为细胞色素b5、热休克70 kDa蛋白8亚型2和组织蛋白酶B。基于2-DE的蛋白质组分析方法与ANN或CART算法相结合,在识别HCC方面表现出令人满意,并揭示了潜在的候选癌症生物标志物。