Identifying genes for establishing a multigenic test for hepatocellular carcinoma surveillance in hepatitis C virus-positive cirrhotic patients.
Identifying genes for establishing a multigenic test for hepatocellular carcinoma surveillance in hepatitis C virus-positive cirrhotic patients.
复制标题
鉴定用于建立多基因检测的基因，用于丙型肝炎病毒阳性肝硬化患者的肝细胞癌监测。
DOI：
10.1158/1055-9965.epi-09-0767
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发表时间：
2009-11
影响因子：
3.8
通讯作者：
Fisher, Robert A.
中科院分区：
文献类型：
--
作者：
Archer, Kellie J.;Mas, Valeria R.;David, Krystle;Maluf, Daniel G.;Bornstein, Karen;Fisher, Robert A.
在这项研究中，我们使用Affymetrix HG-U133A 2.0版本的GeneChips，通过使用L1惩罚逻辑回归模型对高维数据集进行建模，并使用n倍交叉验证估计误差，从而识别能够区分有和没有肝细胞癌（HCC）的肝硬化肝组织的基因。基因表达芯片鉴定的基因包括与癌症发生和进展有重要联系的基因，包括VAMP2、DPP4、CALR、CACNA1C和EGR1。此外，多基因基因表达分类器中选择的分子标记随后使用实时PCR和从gene expression Omnibus下载的独立获得的基因表达微阵列数据集进行验证。本文衍生的多基因分类器与目前用于HCC监测的标准腹部超声检查和血清甲胎蛋白检查表现相似或更好。由于早期HCC诊断增加了治疗选择的可及性，从而提高了生存率，这些分子标记物可能被证明对HCC的早期诊断有用，特别是如果前瞻性验证并转化为可重复和可靠的无创检测的基因产物。
In this study, we used the Affymetrix HG-U133A version 2.0 GeneChips for identifying genes capabable of distinguishing cirrhotic liver tissues with and without hepatocellular carcinoma (HCC) by modeling the high-dimensional dataset using an L1 penalized logistic regression model, with error estimated using N-fold cross-validation. Genes identified by gene expression microarray included those that have important links to cancer development and progression, including VAMP2, DPP4, CALR, CACNA1C, and EGR1. In addition, the selected molecular markers in the multigenic gene expression classifier were subsequently validated using real-time PCR and an independently acquired gene expression microarray dataset downloaded from Gene Expression Omnibus. The multigenetic classifier derived herein performed similarly or better that standard abdominal ultrasonography and serum alpha-fetoprotein, which are currently used for HCC surveillance. Since early HCC diagnosis increases survival by increasing access to therapeutic options, these molecular markers may prove useful for early diagnosis of HCC, especially if prospectively validated and translated into gene products that can be reproducibly and reliably tested non-invasively.