Protein expression profile characteristic to hepatocellular carcinoma revealed by 2D-DIGE with supervised learning
Protein expression profile characteristic to hepatocellular carcinoma revealed by 2D-DIGE with supervised learning
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DOI：
10.1016/j.bbapap.2008.02.011
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发表时间：
2008-05-01
影响因子：
3.2
通讯作者：
Kaneko, Shuichi
中科院分区：
文献类型：
--
作者：
Teramoto, Reiji;Minagawa, Hirotaka;Kaneko, Shuichi
肝细胞癌（HCC）是最常见和侵袭性的人类恶性肿瘤之一。虽然与HCC相关的几个主要风险，如乙型肝炎和/或丙型肝炎病毒感染、黄曲霉毒素B1暴露、饮酒和遗传缺陷已经被发现，但导致HCC发生和发展的分子机制尚未明确。为了降低死亡率和提高治疗效果，检测与肿瘤进展相关的蛋白质是很重要的，这些蛋白质可能是潜在的治疗或诊断靶点。然而，先前的研究尚未揭示HCC细胞、组织学分级与AFP之间的关系。在这里，我们对18例HCC患者进行了二维差异凝胶电泳（2D-DIGE）联合MS。为了不关注单个蛋白质，而是关注与发病机制相关的多种蛋白质，我们引入了基于随机梯度增强（SGB）的监督特征选择，以识别区分HCC/非HCC、中等/良好组织学等级和高甲胎蛋白(AFP)/低甲胎蛋白水平的蛋白质点，而不具有随机性。我们分别检测到18、25和27个与HCC、组织学分级和AFP水平相关的蛋白斑点。我们证实SGB能够识别已知的hcc相关蛋白，如热休克蛋白、碳酸酐酶2。此外，我们鉴定了与HCC组织学分级和AFP水平相关的差异表达蛋白，发现醛酮还原酶1B10 （AKR1B10）与分化良好的HCC相关，角蛋白8 （KRT8）与组织学分级和AFP水平相关，蛋白二硫异构酶相关3 （PDIA3）与HCC和AFP水平相关。我们的初步研究为了解HCC的发病机制、组织学分级和AFP水平提供了新的见解。(c) 2008 Elsevier B.V.版权所有
Hepatocellular carcinoma (HCC) is one of the most common and aggressive human malignancies. Although several major risks related to HCC, e.g., hepatitis B and/or hepatitis C virus infection, aflatoxin B1 exposure, alcohol drinking and genetic defects have been revealed, the molecular mechanisms leading to the initiation and progression of HCC have not been clarified. To reduce the mortality and improve the effectiveness of therapy, it is important to detect the proteins which are associated with tumor progression and may be useful as potential therapeutic or diagnosis targets. However, previous studies have not yet revealed the associations among HCC cells, histological grade and AFP. Here, we performed two-dimensional difference gel electrophoresis (2D-DIGE) combined with MS for 18 HCC patients. To focus not on individual proteins but on multiple proteins associated with pathogenesis, we introduce the supervised feature selection based on stochastic gradient boosting (SGB) for identifying protein spots that discriminate HCC/non HCC, histological grade of moderate/well and high alpha-fetoprotein (AFP)/low AFP level without arbitrariness. We detected 18, 25 and 27 protein spots associated with HCC, histological grade and AFP level, respectively. We confirmed that SGB is able to identify the known HCC-related proteins, e.g., heat shock proteins, carbonic anhydrase 2. Moreover, we identified the differentially expressed proteins associated with histological grade of HCC and AFP level and found that aldo-ketc, reductase 1B10 (AKR1B10) is related to well differentiated HCC, keratin 8 (KRT8) is related to both histological grade and AFP level and protein disulfide isomerase-associated 3 (PDIA3) is associated with both HCC and AFP level. Our pilot study provides new insights on understanding the pathogenesis of HCC, histological grade and AFP level. (c) 2008 Elsevier B.V. All rights reserved.