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鉴定用于预测肝细胞癌患者生存情况的潜在预后微小RNA生物标志物。

Identification of potential prognostic microRNA biomarkers for predicting survival in patients with hepatocellular carcinoma.

作者信息

Liao Xiwen, Zhu Guangzhi, Huang Rui, Yang Chengkun, Wang Xiangkun, Huang Ketuan, Yu Tingdong, Han Chuangye, Su Hao, Peng Tao

机构信息

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, People's Republic of China.

Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People's Republic of China.

出版信息

Cancer Manag Res. 2018 Apr 13;10:787-803. doi: 10.2147/CMAR.S161334. eCollection 2018.

Abstract

BACKGROUND

The aim of the present study was to identify potential prognostic microRNA (miRNA) biomarkers for hepatocellular carcinoma (HCC) prognosis prediction based on a dataset from The Cancer Genome Atlas (TCGA).

MATERIALS AND METHODS

A miRNA sequencing dataset and corresponding clinical parameters of HCC were obtained from TCGA. Genome-wide univariate Cox regression analysis was used to screen prognostic differentially expressed miRNAs (DEMs), and multivariable Cox regression analysis was used for prognostic signature construction. Comprehensive survival analysis was performed to evaluate the prognostic value of the prognostic signature.

RESULTS

Five miRNAs were regarded as prognostic DEMs and used for prognostic signature construction. The five-DEM prognostic signature performed well in prognosis prediction (adjusted < 0.0001, adjusted hazard ratio = 2.249, 95% confidence interval =1.491-3.394), and time-dependent receiver-operating characteristic (ROC) analysis showed an area under the curve (AUC) of 0.765, 0.745, 0.725, and 0.687 for 1-, 2-, 3-, and 5-year HCC overall survival (OS) prediction, respectively. Comprehensive survival analysis of the prognostic signature suggests that the risk score model could serve as an independent factor of HCC and perform better in prognosis prediction than other traditional clinical indicators. Functional assessment of the target genes of hsa-mir-139 and hsa-mir-5003 indicates that they were significantly enriched in multiple biological processes and pathways, including cell proliferation and cell migration regulation, pathways in cancer, and the cyclic adenosine monophosphate (cAMP) signaling pathway.

CONCLUSION

Our study indicates that the novel miRNA expression signature may be a potential prognostic biomarker for HCC patients.

摘要

背景

本研究旨在基于来自癌症基因组图谱(TCGA)的数据集,鉴定用于预测肝细胞癌(HCC)预后的潜在预后微小RNA(miRNA)生物标志物。

材料与方法

从TCGA获得HCC的miRNA测序数据集及相应临床参数。采用全基因组单变量Cox回归分析筛选预后差异表达miRNA(DEM),并采用多变量Cox回归分析构建预后特征。进行综合生存分析以评估预后特征的预后价值。

结果

5个miRNA被视为预后DEM并用于构建预后特征。五DEM预后特征在预后预测中表现良好(校正<0.0001,校正风险比=2.249,95%置信区间=1.491-3.394),且时间依赖性受试者工作特征(ROC)分析显示,对于1年、2年、3年和5年HCC总生存(OS)预测,曲线下面积(AUC)分别为0.765、0.745、0.725和0.687。对预后特征的综合生存分析表明,风险评分模型可作为HCC的独立因素,且在预后预测中比其他传统临床指标表现更好。对hsa-mir-139和hsa-mir-5003靶基因的功能评估表明,它们在多个生物学过程和途径中显著富集,包括细胞增殖和细胞迁移调控、癌症途径以及环磷酸腺苷(cAMP)信号通路。

结论

我们的研究表明,新的miRNA表达特征可能是HCC患者潜在的预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a884/5912208/c11b22902c7b/cmar-10-787Fig1.jpg

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