An epithelial-mesenchymal transition-related 5-gene signature predicting the prognosis of hepatocellular carcinoma patients.
An epithelial-mesenchymal transition-related 5-gene signature predicting the prognosis of hepatocellular carcinoma patients.
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预测肝细胞癌患者预后的上皮间充质转化相关 5 基因特征
DOI：
10.1186/s12935-021-01864-5
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发表时间：
2021-03-12
影响因子：
5.8
通讯作者：
Bi F
中科院分区：
文献类型：
--
作者：
Zhu G;Xia H;Tang Q;Bi F
肿瘤转移是导致肝细胞癌预后不良的主要原因之一。上皮-间充质转化(EMT)与包括肝细胞癌在内的肿瘤转移密切相关。本研究的目的是构建和验证用于预测肝癌患者预后的EMT相关基因特征。方法从肿瘤基因组图谱(TCGA)数据库下载肝癌患者的基因表达数据。基因集浓缩分析(GSEA)发现在正常肝组织和配对肝细胞癌组织中存在明显差异的EMT相关基因。用Cox回归分析建立EMT相关的预后信号，并通过Kaplan-Meier曲线和时间依赖的受试者工作特征(ROC)曲线来评估该信号的性能。建立了包含独立预测因子的诺模图。用实时定量聚合酶链式反应(qRT-PCR)检测HUB基因在肝癌细胞系中的表达水平，并通过功能实验确定PDCD6在肝癌转移中的作用。结果通过单因素和多因素Cox回归分析，构建了与EMT相关的5个基因特征(PDCD6、TCOF1、TRIM28、EZH2和FAM83D)。根据征象将肝癌患者分为高危组和低危组，高危组患者预后较差。时间依赖的ROC和COX回归分析表明，该征象可以准确、独立地预测肝癌的预后。签名的预测能力也在两个外部队列中得到了验证。GSEA结果显示，在高危人群中，PI3K/Akt/mTor、转化生长因子-β/SMAD等多种与肿瘤相关的信号转导通路表达丰富。QRT-PCR结果显示PDCD6、TCOF1和FAM83D在肝癌细胞中高表达。结论EMT相关的5基因标志物可作为预测肝细胞癌患者预后的生物标志物，并可能为肝细胞癌的转移提供新的机制。
BackgroundTumor metastasis is one of the leading reasons of the dismal prognosis of hepatocellular carcinoma (HCC). Epithelial-mesenchymal transition (EMT) is closely associated with tumor metastasis including HCC. The purpose of this study is to construct and validate an EMT-related gene signature for predicting the prognosis of HCC patients.MethodsGene expression data of HCC patients was downloaded from The Cancer Genome Atlas (TCGA) database. Gene set enrichment analysis (GSEA) was performed to found the EMT-related gene sets which were obviously distinct between normal samples and paired HCC samples. Cox regression analysis was used to develop an EMT-related prognostic signature, and the performance of the signature was evaluated by Kaplan–Meier curves and time-dependent receiver operating characteristic (ROC) curves. A nomogram incorporating the independent predictors was established. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of the hub genes in HCC cell lines, and the role of PDCD6 in the metastasis of HCC was determined by functional experiments.ResultsAn EMT-related 5-gene signature (PDCD6, TCOF1, TRIM28, EZH2 and FAM83D) was constructed using univariate and multivariate Cox regression analysis. Based on the signature, the HCC patients were classified into high- and low-risk groups, and patients in high-risk group had a poor prognosis. Time-dependent ROC and Cox regression analyses suggested that the signature could predict HCC prognosis exactly and independently. The predictive capacity of the signature was also validated in two external cohorts. GSEA results showed that many cancer-related signaling pathways such as PI3K/Akt/mTOR pathway and TGF-β/SMAD pathway were enriched in high-risk group. The result of qRT-PCR revealed that PDCD6, TCOF1 and FAM83D were highly expressed in HCC cancer cells. Among them, PDCD6 were found to promote cell migration and invasion.ConclusionThe EMT-related 5-gene signature can serve as a promising prognostic biomarker for HCC patients and may provide a novel mechanism of HCC metastasis.
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影响因子：
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作者：
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影响因子：
25.7
作者：
Xu, Leibo;Beckebaum, Susanne;Cicinnati, Vito R.
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影响因子：
6
作者：
la Cour, JM;Mollerup, J;Berchtold, MW
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Berchtold, MW
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DOI：
10.1016/j.bbrc.2015.01.108
发表时间：
2015-03-06
影响因子：
3.1
作者：
Wang, Dong;Han, Sheng;Li, Xiang-Cheng
通讯作者：
Li, Xiang-Cheng
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影响因子：
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作者：
Jiang, Longyang;Zhao, Lan;Zhao, Lin
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