Identification of metastasis-related microRNAs in hepatocellular carcinoma
Identification of metastasis-related microRNAs in hepatocellular carcinoma
复制标题
肝细胞癌转移相关microRNA的鉴定
DOI：
10.1002/hep.22160
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发表时间：
2008-03-01
期刊：
影响因子：
13.5
通讯作者：
Wang, Xin Wei
中科院分区：
文献类型：
--
作者：
Budhu, Anuradha;Jia, Hu-Liang;Wang, Xin Wei
microRNA（miRNAs）已被用作癌症相关的生物标志物。肝细胞癌（HCC）是一种侵袭性癌症，其预后很差，主要是由于转移和术后复发。我们研究了某些miRNAs的表达是否与HCC转移相关。我们检测了241例HCC患者根治性切除术后482例癌性和非癌性标本的miRNA表达谱。使用监督算法和临床明确定义的131例病例队列，我们建立了一个独特的20-miRNA转移特征，可以显著预测（P < 0.001）原发性HCC组织与无转移的孤立性肿瘤的静脉转移，交叉验证10倍。然而，不能从相应的非癌肝组织中鉴定出显著的miRNAs。生存风险预测分析显示，大多数转移相关的miRNA与生存相关。此外，20-miRNA肿瘤标记在另外110例病例中被验证为生存的显著独立预测因子（P = 0.009），并且与89例早期HCC的生存和复发显著相关（分别为P = 0.022和0.002）。这20种miRNAs可能提供一种简单的分析方法，以帮助识别可能发生转移/复发的HCC患者。此外，这些miRNAs的功能分析可能会提高我们对HCC转移的生物学理解。
MicroRNAs (miRNAs) have been used as cancer-related biomarkers. Hepatocellular carcinoma (HCC) is an aggressive cancer with a dismal outcome largely due to metastasis and postsurgical recurrence. We investigated whether the expression of certain miRNAs are associated with HCC metastasis. We examined the miRNA expression profiles of 482 cancerous and noncancerous specimens from radical resection of 241 patients with HCC. Using a supervised algorithm and a clinically well-defined cohort of 131 cases, we built a unique 20-miRNA metastasis signature that could significantly predict (P < 0.001) primary HCC tissues with venous metastases from metastasis-free solitary tumors with 10-fold cross-validation. However, significant miRNAs could not be identified from the corresponding noncancerous hepatic tissues. A survival risk prediction analysis revealed that a majority of the metastasis-related miRNAs were associated with survival. Furthermore, the 20-miRNA tumor signature was validated in 110 additional cases as a significant independent predictor of survival (P = 0.009) and was significantly associated with both survival and relapse in 89 cases of early stage HCC (P = 0.022 and 0.002, respectively). These 20 miRNAs may provide a simple profiling method to assist in identifying patients with HCC who are likely to develop metastases/recurrence. In addition, functional analysis of these miRNAs may enhance our biological understanding of HCC metastasis.