Identification of Potential Biomarkers From Hepatocellular Carcinoma With MT1 Deletion.
Identification of Potential Biomarkers From Hepatocellular Carcinoma With MT1 Deletion.
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鉴定 MT1 缺失的肝细胞癌的潜在生物标志物
DOI：
10.3389/pore.2021.597527
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Hu Q
中科院分区：
文献类型：
--
作者：
Zhang R;Huang M;Wang H;Wu S;Yao J;Ge Y;Lu Y;Hu Q
背景：肝细胞癌是世界范围内死亡率最高的癌症之一。金属硫蛋白(Metals thioneins，MTS)是一种金属结合蛋白，参与多种生物过程，如金属稳态、解毒和肿瘤发生。拷贝数变异(CNV)在肿瘤的发生、发展中起着重要作用。然而，目前还没有关于MT1CNV在肝细胞癌中作用的研究。方法：采用基于阵列的比较基因组杂交(ACGH)分析方法，获得79例广西肝癌患者的CNV资料。单因素和多因素Cox回归分析MT1缺失对预后的影响。根据基因表达总览数据库(GEO)和肝细胞癌肿瘤基因组图谱(TCGA-LIHC)筛选差异表达基因(DEG)。然后对DEGS进行功能和途径丰富分析、蛋白质相互作用(PPI)和HUB基因选择。最后，通过免疫组织化学、组织表达和预后分析对HUB基因进行验证。结果：MT1基因缺失可影响肝细胞癌的预后，并可作为独立的预后因素。共筛查常见疾病147例。分子复合体检测(MCODE)发现的最显著的DEG簇表明，4个MT1基因的表达下调。MT1X和其他5个HUB基因(TTK、Bub1、CyP3A4、NR1I2、CyP8B1)与肝细胞癌的预后相关。TTK可能影响MT1缺失和非缺失的肝细胞癌的预后。NR1I2、CYP8B1和Bub1与MT1缺失的肝细胞癌的预后相关。结论：在目前的研究中，我们证明MT1缺失可以作为肝细胞癌的一个独立预后因素。我们通过处理微阵列数据鉴定了TTK、Bub1、NR1I2、CyP8B1，首次揭示了MT1缺失在肝癌中的潜在作用，MT1缺失可能影响肝癌中基因的表达，这些可能是MT1缺失的潜在生物标志物。
Background: Hepatocellular carcinoma (HCC) is one of the deadliest cancers worldwide. Metallothioneins (MTs) are metal-binding proteins involved in multiple biological processes such as metal homeostasis and detoxification, as well as in oncogenesis. Copy number variation (CNV) plays a vital role in pathogenesis and carcinogenesis. Nevertheless, there is no study on the role of MT1 CNV in HCC. Methods: Array-based Comparative Genomic Hybridization (aCGH) analysis was performed to obtain the CNV data of 79 Guangxi HCC patients. The prognostic effect of MT1-deletion was analyzed by univariate and multivariate Cox regression analysis. The differentially expressed genes (DEGs) were screened based on The Gene Expression Omnibus database (GEO) and the Liver Hepatocellular Carcinoma of The Cancer Genome Atlas (TCGA-LIHC). Then function and pathway enrichment analysis, protein-protein interaction (PPI) and hub gene selection were applied on the DEGs. Lastly, the hub genes were validated by immunohistochemistry, tissue expression and prognostic analysis. Results: The MT1-deletion was demonstrated to affect the prognosis of HCC and can act as an independent prognostic factor. 147 common DEGs were screened. The most significant cluster of DEGs identified by Molecular Complex Detection (MCODE) indicated that the expression of four MT1s were down-regulated. MT1X and other five hub genes (TTK, BUB1, CYP3A4, NR1I2, CYP8B1) were associated with the prognosis of HCC. TTK, could affect the prognosis of HCC with MT1-deletion and non-deletion. NR1I2, CYP8B1, and BUB1 were associated with the prognosis of HCC with MT1-deletion. Conclusions: In the current study, we demonstrated that MT1-deletion can be an independent prognostic factor in HCC. We identified TTK, BUB1, NR1I2, CYP8B1 by processing microarray data, for the first time revealed the underlying function of MT1 deletion in HCC, MT1-deletion may influence the gene expression in HCC, which may be the potential biomarkers for HCC with MT1 deletion.
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影响因子：
14.9
作者：
Ritchie ME;Phipson B;Wu D;Hu Y;Law CW;Shi W;Smyth GK
通讯作者：
Smyth GK
影响因子：
4.6
作者：
Harmsen, S.;Meijerman, I.;Schellens, J. H. M.
通讯作者：
Schellens, J. H. M.
影响因子：
11.5
作者：
Gupta, Divya;Venkatesh, Madhukumar;Mani, Sridhar
通讯作者：
Mani, Sridhar
DOI：
10.1098/rstb.2011.0072
发表时间：
2011-12-27
期刊：
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
影响因子：
--
作者：
Musacchio A
通讯作者：
Musacchio A
影响因子：
--
作者：
Chin CH;Chen SH;Wu HH;Ho CW;Ko MT;Lin CY
通讯作者：
Lin CY