Li Lei, Liu Shuiping, Peng Li, Zhang Yapeng, Zhang Yaqin, Zeng Haiyan, Li Guancheng, Zhang Chaoyang
Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, China.
School of Basic Medical Science, Central South University, Changsha, China.
Arch Med Sci. 2019 Nov 12;18(6):1582-1595. doi: 10.5114/aoms.2019.89707. eCollection 2022.
Hepatocellular carcinoma (HCC) is a common malignant tumour of the digestive system, which is a threat to public health. The purpose of this study was to investigate the featured genes and pathways of HCC from a bioinformatics database, and verify their correlation with diagnosis and prognosis of HCC.
We downloaded the gene expression profile on HCC from the Gene Expression Omnibus (GEO), and software R was used to identify differentially expressed lncRNA (DEL). The target genes of the lncRNA were further predicted by using a cluster database and molecular interaction database. Subsequently, a combined interaction network of target genes was constructed using the Cytoscape platform with preliminary verification at the level of different databases, cell lines, and tissues. Finally, we explored the effectiveness of TUG1 and its target genes on the diagnosis and prognosis of HCC by univariate Cox analysis and survival analysis.
A total of four DELs were identified and the most remarkably up-regulated lncRNA was TUG1, which included 12 high-confidence target genes. Moreover, we found that the expression changes of TUG1 and its target genes in different databases, cell lines, and liver cancer tissues were consistent with the prediction. The high expression of TUG1 and its target genes could significantly predict the shorter survival time of HCC patients, among which NCAPG, MCM6, PIGC, PEA15, and RACGAP1 have significant diagnostic value for HCC (AUC > 0.9).
This study provides a starting point for the screening of therapeutically relevant targets in HCC. Further experiment should be conducted to verify our findings.
肝细胞癌(HCC)是消化系统常见的恶性肿瘤,对公众健康构成威胁。本研究旨在从生物信息学数据库中探究HCC的特征基因和通路,并验证它们与HCC诊断及预后的相关性。
我们从基因表达综合数据库(GEO)下载了HCC的基因表达谱,并使用R软件鉴定差异表达的lncRNA(DEL)。通过聚类数据库和分子相互作用数据库进一步预测lncRNA的靶基因。随后,使用Cytoscape平台构建靶基因的联合相互作用网络,并在不同数据库、细胞系和组织水平进行初步验证。最后,通过单因素Cox分析和生存分析探究TUG1及其靶基因对HCC诊断和预后的有效性。
共鉴定出4个DEL,其中上调最显著的lncRNA是TUG1,它包含12个高可信度靶基因。此外,我们发现TUG1及其靶基因在不同数据库、细胞系和肝癌组织中的表达变化与预测一致。TUG1及其靶基因的高表达可显著预测HCC患者较短的生存时间,其中NCAPG、MCM6、PIGC、PEA15和RACGAP1对HCC具有显著诊断价值(AUC>0.9)。
本研究为HCC治疗相关靶点的筛选提供了一个起点。应进行进一步实验以验证我们的发现。