Integrative analysis of h-prune as a potential therapeutic target for hepatocellular carcinoma
Integrative analysis of h-prune as a potential therapeutic target for hepatocellular carcinoma
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h-prune作为肝细胞癌潜在治疗靶点的综合分析
DOI：
10.1016/j.ebiom.2019.01.001
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发表时间：
2019-03-01
期刊：
影响因子：
11.1
通讯作者：
Zeng, Yong
中科院分区：
文献类型：
--
作者：
Liao, Haotian;Liao, Mingheng;Zeng, Yong
背景：果蝇prune蛋白（h-prune）在调节肿瘤转移中起重要作用。然而，h-prune的临床相关性及其在调节肝细胞癌（HCC）的潜在机制仍然知之甚少：在这项研究中，我们使用组织芯片（TMA）包含304个HCC肿瘤样本，以评估h-prune的表达及其与预后的相关性。采用RT-PCR方法，对肝癌组织中h-prune基因的表达情况进行了分析，并对h-prune基因在肝癌组织中的表达情况进行了比较。h-prune的高表达与较差的OS和DFS结局相关。多因素分析显示h-prune表达是影响OS和DFS的独立危险因素。基因富集分析显示，h-prune-high患者中细胞增殖、DNA甲基化和经典Wnt信号通路的基因标签富集。值得注意的是，体细胞突变分析表明，RB 1和RPS 6 KA 3的较高突变负荷可以在h-修剪-高患者中观察到。此外，综合分析揭示了h-prune表达和表观遗传学变化之间的强相关性。Interpretation：本研究突出了h-prune在预测肝癌患者预后中的临床价值及其在促进肝癌发生中的重要作用。(c)2019年，任作家。由Elsevier B. V.发布。这是CC BY-NC-ND许可证下的开放获取文章（http：//creativecommons.org/licenses/by-nc-nd/4.0/）。
Background: Drosophila prune protein (h-prune) has been proved to play an essential role in regulating tumor metastasis. However, the clinical relevance of h-prune and its potential mechanism in regulating hepatocellular carcinoma (HCC) are still poorly understood.Methods: In this study, we used tissue microarrays (TMA) containing 304 HCC tumor samples to evaluate the expression of h-prune and its correlation with prognosis. Data of RNAseq, mutation profiles, copy number variation (CNV), miRNAseq and methylation array from The Cancer Genome Atlas (TCGA) dataset were adopted to analyze the distinctive genomic patterns associated with h-prune expression.Results: By using TMA, we found increased expression of h-prune in HCC tumor cells compared with adjacent normal tissues. Higher expression of h-prunewas correlated with poorer OS and DFS outcomes. In addition, multivariate analysis showed that h-prune expressionwas an independent risk factor for both OS and DFS. Gene enrichment analysis showed that the gene signatures of cell proliferation, DNA methylation and canonical Wnt signaling pathway were enriched in h-prune-high patients. Notably, somatic mutation analysis demonstrated that higher mutation burden of RB1 and RPS6KA3 could be observed in h-prune-high patients. Moreover, integrative analysis revealed a strong correlation between h-prune expression and epigenetic changes.Interpretation: This study has highlighted the clinical value of h-prune in predicting the prognosis of HCC patients and its essential role in promoting tumorigenesis of HCC. (c) 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).