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首页> 外文期刊>Drug Target Insights >Identification of the possible therapeutic targets in the insulin-like growth factor 1 receptor pathway in a cohort of Egyptian hepatocellular carcinoma complicating chronic hepatitis C type 4
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Identification of the possible therapeutic targets in the insulin-like growth factor 1 receptor pathway in a cohort of Egyptian hepatocellular carcinoma complicating chronic hepatitis C type 4

机译：在埃及肝细胞癌群组中的胰岛素样生长因子1受体途径中的可能治疗靶标鉴定4型慢性丙型肝炎4型

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ABSTRACT Background: Molecular targeted drugs are the first line of treatment of advanced hepatocellular carcinoma (HCC) due to its chemo- and radioresistant nature. HCC has several well-documented etiologic factors that drive hepatocarcinogenesis through different molecular pathways. Currently, hepatitis C virus (HCV) is a leading cause of HCC. Therefore, we included a unified cohort of HCV genotype 4-related HCCs to study the expression levels of genes involved in the insulin-like growth factor 1 receptor (IGF1R) pathway, which is known to be involved in all aspects of cancer growth and progression. Aim: Determine the gene expression patterns of IGF1R pathway genes in a cohort of Egyptian HCV-related HCCs. Correlate them with different patient/tumor characteristics. Determine the activity status of involved pathways. Methods: Total ribonucleic acid (RNA) was extracted from 32 formalin-fixed paraffin-embedded tissues of human HCV-related HCCs and 6 healthy liver donors as controls. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) using RT ~(2) Profiler PCR Array for Human Insulin Signaling Pathway was done to determine significantly up- and downregulated genes with identification of most frequently coregulated genes, followed by correlation of gene expression with different patient/tumor characteristics. Finally, canonical pathway analysis was performed using the Ingenuity Pathway Analysis software. Results: Six genes – AEBP1, AKT2, C-FOS, PIK3R1, PRKCI, SHC1 – were significantly overexpressed. Thirteen genes?– ADRB3, CEBPA, DUSP14, ERCC1, FRS3, IGF2, INS, IRS1, JUN, MTOR, PIK3R2, PPP1CA, RPS6KA1?– were significantly underexpressed. Several differentially expressed genes were related to different tumor/patient characteristics. Nitric oxide and reactive oxygen species production pathway was significantly activated in the present cohort, while the growth hormone signaling pathway was inactive. Conclusions: The gene expression patterns identified in this study may serve as possible therapeutic targets in HCV-related HCCs. The most frequently coregulated genes may serve to guide combined molecular targeted therapies. The IGF1R pathway showed evidence of inactivity in the present cohort of HCV-related HCCs, so targeting this pathway in therapy may not be effective.
机译：摘要背景：由于其化学和放射性的性质，分子靶向药物是前一种治疗晚期肝细胞癌（HCC）的一系列治疗。 HCC具有几种记录的良好记录的病因因子，可通过不同的分子途径驱动肝癌发生。目前，丙型肝炎病毒（HCV）是HCC的主要原因。因此，我们包括统一的HCV基因型4相关的HCC队列，以研究胰岛素样生长因子1受体（IGF1R）途径中涉及的基因的表达水平，这已知是癌症生长和进展的所有方面。目的：确定IGF1R途径基因的基因表达模式在埃及HCV相关的HCC队中。将它们与不同的患者/肿瘤特征相关联。确定涉及途径的活动状态。方法：将总核糖核酸（RNA）从32例福尔马林固定的石蜡组织中提取，作为对照的62例福尔马林固定的石蜡组织和6种健康肝脏供体。用于人胰岛素信号传导途径的RT〜（2）分析仪PCR阵列的定量逆转录聚合酶链反应（QRT-PCR）以确定显着上调和下调的基因，鉴定最常常用的基因，然后与基因表达相关不同的患者/肿瘤特征。最后，使用Ingenuey途径分析软件进行规范途径分析。结果：六个基因 - AEBP1，AKT2，C-FOS，PIK3R1，PRKCI，SHC1 - 显着过表达。十三基因？ - ADRB3，CEBPA，DUSP14，ERCC1，FRS3，IGF2，INS，IRS1，JUM，MTOR，PIK3R2，PPP1CA，RPS6KA1？ - 显着曝光出来。几种差异表达基因与不同的肿瘤/患者特征有关。在目前的队列中显着激活一氧化氮和反应性氧物质生产途径，而生长激素信号通路是无活性的。结论：本研究中鉴定的基因表达模式可作为HCV相关的HCCs中的可能治疗靶标。最常见的重铸基因可用于引导组合分子靶向疗法。 IGF1R途径显示出目前与HCV相关的HCC群体中不活动的证据，因此靶向治疗中的该途径可能无效。

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