Identification of hub genes in hepatocellular carcinoma using integrated bioinformatic analysis
Identification of hub genes in hepatocellular carcinoma using integrated bioinformatic analysis
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DOI：
10.18632/aging.102969
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发表时间：
2020-03-31
期刊：
影响因子：
5.2
通讯作者：
Lu, Ligong
中科院分区：
文献类型：
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作者：
Hua, Shengni;Ji, Zhonghua;Lu, Ligong
肝细胞癌进展的分子机制在很大程度上仍不清楚。在这里，我们基于三个基因表达总览数据集和癌症基因组图谱(TCGA)队列，确定了176个在肝癌组织中普遍上调的基因。我们综合了生存和甲基化分析，以进一步获得12个上调的基因进行验证。这些基因在肝细胞癌组织中均有转录和蛋白水平的高表达，其表达水平与肿瘤分级和分期有关。所有标记物的表达与肝细胞癌患者的总体和无病生存期呈负相关。这些HUB基因大多能促进肝细胞癌的增殖和/或转移。这12个HUB基因也过度表达，在许多其他类型的癌症中具有很强的预后价值。甲基化和基因拷贝数分析表明，这些Hub基因的上调可能是由于低甲基化或基因拷贝数增加所致。此外，三个基因KPNA2、MCM3和LRRC1的甲基化水平与肝细胞癌的临床特征相关。此外，大多数HUB基因的表达水平与肝细胞癌微环境中免疫细胞的浸润有关。最后，我们确定了三个上调的基因(KPNA2、TARBP1和RNASE_2A)，它们可以全面和准确地为肝癌患者提供诊断和预后价值。
The molecular mechanisms underlying hepatocellular carcinoma (HCC) progression remain largely undefined. Here, we identified 176 commonly upregulated genes in HCC tissues based on three Gene Expression Omnibus datasets and The Cancer Genome Atlas (TCGA) cohort. We integrated survival and methylation analyses to further obtain 12 upregulated genes for validation. These genes were overexpressed in HCC tissues at the transcription and protein levels, and increased mRNA levels were related to higher tumor grades and cancer stages. The expression of all markers was negatively associated with overall and disease-free survival in HCC patients. Most of these hub genes can promote HCC proliferation and/or metastasis. These 12 hub genes were also overexpressed and had strong prognostic value in many other cancer types. Methylation and gene copy number analyses indicated that the upregulation of these hub genes was probably due to hypomethylation or increased gene copy numbers. Further, the methylation levels of three genes, KPNA2, MCM3, and LRRC1, were associated with HCC clinical features. Moreover, the levels of most hub genes were related to immune cell infiltration in HCC microenvironments. Finally, we identified three upregulated genes (KPNA2, TARBP1, and RNASEH2A) that could comprehensively and accurately provide diagnostic and prognostic value for HCC patients.