利用癌旁组织中基因表达的秩序关系识别肝癌的早期诊断特征  

Identifying Markers of Hepatocellular Carcinoma for Early Diagnosis Based on the Relative Expression Orders of Genes in Cirrhosis Tissues Adjacent to Carcinoma

作　　者：章琳[1] 郝春香[1] 陈蓓蓓[2] 廖之君[3] 郭政[1,3] 

机构地区：[1]电子科技大学生命学院生物信息中心,成都610054 [2]哈尔滨医科大学生物信息科学与技术学院,哈尔滨150086 [3]福建医科大学基础医学院生物信息学实验室,福州350004

出　　处：《生物物理学报》2013年第8期614-623,共10页Acta Biophysica Sinica

基　　金：国家自然科学基金项目(30970668;81071646;91029717;81201702);福建省科技厅青年人才基金项目(2008F3045)~~

摘　　要：目前,对于肝癌(hepatocellular carcinoma,HCC)早期检测中放射成像技术无法确定的结节,通常需要通过活检取样来进行组织病理学鉴定。然而,一些早期肝癌组织中所呈现的病理改变微小难辨,活检取样时也经常会出现未取到癌组织而漏检的情况。针对这些临床上肝癌早期诊断的困难,同时为了应对基因表达谱检测批次效应等对分类结果的影响,作者提出了利用癌旁组织中基因表达的秩序关系来鉴别早期肝癌及癌前病变的方法。首先找出在肝癌患者的肝硬化组织(cirrhosis tissue in patients with HCC,wHCC)和非肝癌患者的肝硬化组织(cirrhosis tissue in patients without HCC,woHCC)间基因表达值的相对秩序发生逆转的基因对,然后,借用大样本的肝癌组织表达谱数据筛选出HCC及wHCC中表达相对秩序一致的基因对,再基于这些基因对发展能将HCC、wHCC与woHCC进行鉴别的分类器。结果显示,该分类器对来自不同平台、不同实验室的验证集都有稳健的分类能力,可以用于早期肝癌的辅助鉴别诊断。Currently, small equivocal liver lesions detected by imaging techniques need biopsy confirmation in early diagnosis for hepatocellular carcinoma （HCC）. However, pathologic change can be indistinguishable for pathologists and one cannot be certain that the sample did indeed come from the lesion in biopsy when lesion is so small in early HCC. To tackle the clinical difficulties in diagnosis of early hepatocellular carcinoma and to reduce the impact of microarray experimental batch effects on classification results, the authors proposed a method to identify early HCC and precancerous lesions based on the relative gene expressions orders of cirrhosis tissue adjacent to HCC. Firstly, gene pairs with opposite relative expression orders in cirrhosis tissues between patients with and without HCC were detected, from which pairs having the same relative expression orders in both carcinoma and cirrhosis tissues in patients with HCC were then filtered out using large scale HCC samples. Finally, a classifier for discriminating HCC tissues and cirrhosis tissues adjacent to HCC from the cirrhosis tissues in patients without HCC was built based on the filtered pairs. The results showed that the classifier showed robust classification performances in datasets extracted from different platforms and different laboratories, which could serve as an effective tool to aid early HCC diagnosis.

关 键 词：肝癌 癌旁组织 肝硬化 诊断 基因表达 

分 类 号：Q612[生物学—生物物理学]