A novel microRNAs expression signature for hepatocellular carcinoma diagnosis and prognosis.
A novel microRNAs expression signature for hepatocellular carcinoma diagnosis and prognosis.
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用于肝细胞癌诊断和预后的新型 microRNA 表达特征
DOI：
10.18632/oncotarget.14452
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发表时间：
2017-01-31
期刊：
影响因子：
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通讯作者：
He Z
中科院分区：
文献类型：
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作者：
Lu M;Kong X;Wang H;Huang G;Ye C;He Z
本研究旨在通过大样本队列分析，确定用于肝细胞癌（HCC）诊断和生存的预后microRNAs（miRNAs）生物标志物。HCC患者队列数据从癌症基因组图谱下载，包括配对的HCC和相邻的非癌组织。采用受试者工作特征曲线法，根据microRNA表达水平对癌组织和非癌组织进行分类。对异常microRNA表达水平进行排序，并建立预后miRNAs签名模型。采用Kaplan-Meier生存率分析各危险因素之间的差异。该研究通过比较癌症样本和非癌症样本显示了33个miRNA签名，其中11个下调，22个上调。最高分类正确率达98.7%。五种microRNA，hsa-mir-3677，hsa-mir-421，hsa-mir-326，hsa-mir-424和hsa-mir-511-2，与患者生存显著相关。生存率和生存时间与降低miRNAs指数呈负相关。在低危组中，超过70%的患者生存5年，而在高危组中，无患者生存超过5年。miR-424、miR-326和miR-511可作为HCC诊断的生物标志物。通过京都基因与基因组百科全书途径分析和Gene Ontology注释，发现这5种miRNAs与溶酶体途径和D-谷氨酰胺和D-谷氨酸代谢途径显著相关。结论：5种miRNAs表达特征可作为HCC预后和诊断的生物标志物。
This study aims to identify prognostic microRNAs (miRNAs) biomarkers for diagnosis and survival of hepatocellular carcinoma (HCC) based on large patients cohort analysis. HCC patient cohort data were downloaded from The Cancer Genome Atlas, including paired HCC and adjacent non-cancer tissues. Receiver operating characteristic curve method was used to classify cancer and non-cancer tissues according to microRNAs expression levels. The aberrant microRNAs expression level were ranked and risked for building a prognostic miRNAs signature model. Kaplan–Meier survival was used to analyze the differences among various risk factors in accordance with miRNAs ranking scores. The study showed 33-miRNA signature, 11 were down-regulated and 22 were up-regulated through comparison between cancer samples and non-cancer samples. The maximum correct classification rate is up to 98.7%. Five microRNAs, hsa-mir-3677, hsa-mir-421, hsa-mir-326, hsa-mir-424 and hsa-mir-511-2, significantly correlated with patient survival. The survival rate and time negatively associated with lowering miRNAs index. In the low risk group, over 70% patients showed 5 years survival, while none patients survived longer than 5 years in the high risk group. MiR-424, miR-326 and miR-511 could be applied for HCC diagnostic biomarkers. These five miRNAs were significantly associated with lysosome pathway and D-Glutamine and D-glutamate metabolism pathway via Kyoto Encyclopedia of Genes and Genomes pathway analysis and Gene Ontology annotation. Conclusively, the five miRNAs expression signature could be used as HCC prognostic and diagnostic biomarkers.