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通过综合生物信息学分析鉴定肝癌中的模块和新型预后生物标志物。

Identification of modules and novel prognostic biomarkers in liver cancer through integrated bioinformatics analysis.

机构信息

Department of Hepatobiliary Surgery, People's Hospital of Yichun City, China.

Department of Liver Diseases, People's Hospital of Yichun City, China.

出版信息

FEBS Open Bio. 2020 Nov;10(11):2388-2403. doi: 10.1002/2211-5463.12983. Epub 2020 Oct 27.

Abstract

Liver cancer is a common malignant tumor with poor prognosis. Due to the lack of specific clinical manifestations at early stages, most patients are already at advanced stages of the disease by the time of diagnosis. Identification of novel biomarkers for liver cancer may thus enable earlier detection, improving outcome. MicroRNAs (miRNAs) are small endogenous noncoding RNAs of 18-22 nucleotides in length, which have a regulatory role in the expression of target proteins. Increased evidence suggests that miRNAs are abnormally expressed in a variety of cancer malignancies. Here, we combined RNA sequencing data and clinical information from The Cancer Genome Atlas Liver Hepatocellular Carcinoma database for weighted gene coexpression network analysis to identify potential miRNA prognostic biomarkers. We constructed nine coexpression modules, allowing us to identify that miR-105-5p, miR-767-5p, miR-1266-5p, miR-4746-5p, miR-500a-3p, miR-1180-3p and miR-139-5p are significantly associated with liver cancer prognosis. We found that these miRNAs exhibit significant association with prognosis of patients with liver cancer and confirmed the expression of these miRNAs in liver cancer tissues. Multivariate Cox regression analysis showed that miR-105-5p and miR-139-5p may be considered as independent factors. In summary, here we report that seven miRNAs have potential value as prognostic biomarkers of liver cancer.

摘要

肝癌是一种常见的恶性肿瘤,预后较差。由于早期缺乏特异性的临床表现,大多数患者在诊断时已经处于疾病的晚期。因此,鉴定肝癌的新型生物标志物可能有助于早期发现,改善预后。微小 RNA(miRNA)是长度为 18-22 个核苷酸的小内源性非编码 RNA,在靶蛋白的表达中具有调节作用。越来越多的证据表明,miRNA 在多种癌症恶性肿瘤中异常表达。在这里,我们结合 RNA 测序数据和来自癌症基因组图谱肝脏肝癌数据库的临床信息,进行加权基因共表达网络分析,以鉴定潜在的 miRNA 预后生物标志物。我们构建了九个共表达模块,使我们能够识别出 miR-105-5p、miR-767-5p、miR-1266-5p、miR-4746-5p、miR-500a-3p、miR-1180-3p 和 miR-139-5p 与肝癌预后显著相关。我们发现这些 miRNA 与肝癌患者的预后显著相关,并证实了这些 miRNA 在肝癌组织中的表达。多变量 Cox 回归分析显示,miR-105-5p 和 miR-139-5p 可能被视为独立因素。总之,在这里我们报告了七种 miRNA 作为肝癌预后生物标志物具有潜在价值。

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