Transcriptome analysis of liver cancer: ready for the clinic?
Transcriptome analysis of liver cancer: ready for the clinic?
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DOI：
10.1016/j.jhep.2009.02.007
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发表时间：
2009-05
影响因子：
25.7
通讯作者：
Thorgeirsson SS
中科院分区：
文献类型：
--
作者：
Wang XW;Thorgeirsson SS
识别在接受肝细胞癌潜在治愈治疗后复发风险最大的患者是一项挑战。这些高危患者可以接受新的干预措施。在肝细胞癌患者中开发基于基因组的预后预测因子的一个障碍是缺乏对固定组织（而不是冷冻组织）进行全基因组表达谱分析的方法。我们的目的是证明在福尔马林固定的石蜡包埋组织中对6000多个人类基因进行基因表达谱分析的可行性。我们将该方法应用于来自四个系列患者的307例肝细胞癌患者的组织，以发现和验证与生存相关的基因表达特征。福尔马林固定、石蜡包埋组织的表达谱方法非常有效：来自90%患者的样本产生了高质量的数据，包括已存档超过24年的样本。肿瘤组织的基因表达谱未能产生与生存的显着关联。相比之下，在来自82名日本患者的组织样本训练集中，周围非肿瘤肝组织的特征与生存率高度相关，并且在来自美国和欧洲的225名患者的独立组的组织中验证了签名（P=0.04）。我们已经证明了福尔马林固定，石蜡包埋组织的全基因组表达谱的可行性，并表明，一个可重复的基因表达签名与生存相关的肝细胞癌患者的肿瘤相邻的肝组织中存在。
It is a challenge to identify patients who, after undergoing potentially curative treatment for hepatocellular carcinoma, are at greatest risk for recurrence. Such high-risk patients could receive novel interventional measures. An obstacle to the development of genome-based predictors of outcome in patients with hepatocellular carcinoma has been the lack of a means to carry out genomewide expression profiling of fixed, as opposed to frozen, tissue. We aimed to demonstrate the feasibility of gene-expression profiling of more than 6000 human genes in formalin-fixed, paraffin-embedded tissues. We applied the method to tissues from 307 patients with hepatocellular carcinoma, from four series of patients, to discover and validate a gene-expression signature associated with survival. The expression-profiling method for formalin-fixed, paraffin-embedded tissue was highly effective: samples from 90% of the patients yielded data of high quality, including samples that had been archived for more than 24 years. Gene-expression profiles of tumor tissue failed to yield a significant association with survival. In contrast, profiles of the surrounding nontumoral liver tissue were highly correlated with survival in a training set of tissue samples from 82 Japanese patients, and the signature was validated in tissues from an independent group of 225 patients from the United States and Europe (P=0.04). We have demonstrated the feasibility of genomewide expression profiling of formalin-fixed, paraffin-embedded tissues and have shown that a reproducible gene-expression signature correlated with survival is present in liver tissue adjacent to the tumor in patients with hepatocellular carcinoma.