Cancer-associated molecular signature in the tissue samples of patients with cirrhosis
Cancer-associated molecular signature in the tissue samples of patients with cirrhosis
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DOI：
10.1002/hep.20053
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发表时间：
2004-02-01
期刊：
影响因子：
13.5
通讯作者：
Wang, XW
中科院分区：
文献类型：
--
作者：
Kim, JW;Ye, QH;Wang, XW
几种类型的侵袭性癌症，包括肝细胞癌（HCC），通常作为多灶性原发性肿瘤出现。这表明在孤立性肿瘤形成之前，非癌组织中癌前病变的发生率很高。通过互补DNA（cDNA）微阵列检查来自各种病因的肝硬化患者的组织样本的信使RNA表达谱表明，它们可以大致分为两大类。一组包括B和C型肝炎病毒感染、血色病和威尔逊病。另一组主要包括酒精性肝病、自身免疫性肝炎和原发性胆汁性肝硬化。通过交叉验证的留一法机器学习算法对这两组进行分析，揭示了包含556个区分基因的分子特征（P < .001）。值得注意的是，该标签中的273个基因（49%）在HCC中也发生了显著改变（P <0.001）。以前已知许多基因与HCC相关。通过将这组基因与来自163名HCC患者、56名肺癌患者和38名乳腺癌患者的额外独立肿瘤组织样本进行匹配，273个基因签名被验证为癌症相关基因。根据这个特征，30个基因在来自肝硬化高危个体和HCC患者的组织样本中发生了最显著的改变。其中12个基因编码血清中的分泌蛋白。总之，我们在肝硬化患者的组织样本中发现了一个独特的基因特征，它可以作为诊断高危人群中HCC早期发作的候选标志物，并可以指导化学预防的新策略。
Several types of aggressive cancers, including hepatocellular carcinoma (HCC), often arise as a multifocal primary tumor. This suggests a high rate of premalignant changes in noncancerous tissue before the formation of a solitary tumor. Examination of the messenger RNA expression profiles of tissue samples derived from patients with cirrhosis of various etiologies by complementary DNA (cDNA) microarray indicated that they can be grossly separated into two main groups. One group included hepatitis B and C virus infections, hemochromatosis, and Wilson's disease. The other group contained mainly alcoholic liver disease, autoimmune hepatitis, and primary biliary cirrhosis. Analysis of these two groups by the cross-validated leave-one-out machine-learning algorithms revealed a molecular signature containing 556 discriminative genes (P < .001). It is noteworthy that 273 genes in this signature (49%) were also significantly altered in HCC (P < .001). Many genes were previously known to be related to HCC. The 273-gene signature was validated as cancer-associated genes by matching this set to additional independent tumor tissue samples from 163 patients with HCC, 56 patients with lung carcinoma, and 38 patients with breast carcinoma. From this signature, 30 genes were altered most significantly in tissue samples from high-risk individuals with cirrhosis and from patients with HCC. Among them, 12 genes encoded secretory proteins found in sera. In conclusion, we identified a unique gene signature in the tissue samples of patients with cirrhosis, which may be used as candidate markers for diagnosing the early onset of HCC in high-risk populations and may guide new strategies for chemoprevention.