Gene Expression Profiling Unravels Hepatitis C Virus (HCV) Infection-induced Temporal Alteration of Gene Expression in Hepatocellular Carcinoma (HCC)

A. S.R.
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Abstract

Hepatitis C virus-induced liver cirrhosis and hepatocellular Carcinoma (HCC) is a global health concern. Underlying molecular mechanism of HCV-induced-HCC by temporal expression mRNA profiling of mock and HCV-infected Huh7.5.1dif cells was unraveled. A catalogue of bio-markers of HCC was analyzed to interpret the clinical relevance of the bio-markers. The percentage of over-expression and co-occurrence for targeted bio-markers within The Cancer Genomic Atlas (TCGA) were mapped using cBioPortal for cancer genomics. Spotting of differentially expressed genes (DEGs) and related temporal pathways enrichment analysis was accomplished employing MATLAB functions (e.g. mattest). Module analysis of the designed co-expression network using Cytoscape software was carried out. The overall expression of targeted biomarkers was recorded in 60% of the cases. Significantly overexpressed biomarkers recognized were CLK2, E2F5, CDK5, E2F3, MCM3, PCNA and CDK4. CCNB2, CLK2, CDK4, CDC7, E2F3, PCNA, and MCM3 predominantly controlled the co-expression of the listed bio-markers. After the initial phase of infection with a detrimental expression changing pattern, stability in expression followed by consistency in the level of expression of a set of genes was observed. Over-expressed screened biomarkers encompass the potential to be the candidate molecular target for surveillance, diagnosis and therapy of fetal HCV- induced-HCC.
基因表达谱揭示丙型肝炎病毒(HCV)感染诱导的肝细胞癌(HCC)基因表达的时间改变
丙型肝炎病毒引起的肝硬化和肝细胞癌(HCC)是一个全球性的健康问题。通过模拟和感染hcv的Huh7.5.1dif细胞的时间表达mRNA谱,揭示了hcv诱导hcc的潜在分子机制。我们分析了HCC的生物标志物目录,以解释生物标志物的临床相关性。使用cbiopportal进行癌症基因组学研究,绘制癌症基因组图谱(TCGA)中靶向生物标记物的过表达和共出现百分比。利用MATLAB函数(如mattest)完成差异表达基因(deg)的定位和相关时间通路的富集分析。利用Cytoscape软件对所设计的共表达网络进行模块分析。在60%的病例中记录了目标生物标志物的总体表达。已知的显著过表达的生物标志物有CLK2、E2F5、CDK5、E2F3、MCM3、PCNA和CDK4。CCNB2、CLK2、CDK4、CDC7、E2F3、PCNA和MCM3主要控制所列生物标志物的共表达。在具有有害表达变化模式的感染初始阶段之后,观察到一组基因表达水平的稳定性和一致性。筛选过表达的生物标志物有可能成为胎儿HCV诱导的hcc监测、诊断和治疗的候选分子靶点。
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