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有潜力的候选尿微小RNA生物标志物用于埃及丙型肝炎病毒高危患者肝细胞癌的早期检测

Promising Candidate Urinary MicroRNA Biomarkers for the Early Detection of Hepatocellular Carcinoma among High-Risk Hepatitis C Virus Egyptian Patients.

作者信息

Abdalla Moemen Ak, Haj-Ahmad Yousef

机构信息

Centre for Biotechnology, Brock University, St. Catharines, ON, L2S 3A1, Canada.

出版信息

J Cancer. 2012;3:19-31. doi: 10.7150/jca.3.19. Epub 2011 Dec 9.

Abstract

MicroRNAs (miRNA) are small endogenously expressed non-coding RNAs that negatively regulate expression of protein-coding genes at the translational level. Accumulating evidence, such as aberrant expression of miRNAs, suggests that they play a role in the development of cancer. They have been identified in various tumor types, demonstrating that different sets of miRNAs are usually deregulated in different cancers. To identify the miRNA signatures specific for Hepatitis C virus (HCV)-associated Hepatocellular carcinoma (HCC), miRNA expression profiling of 32 HCC post-HCV infected, 74 HCV-positive and 12 control individuals was carried out using whole genome expression profiling. Differential expression of two individual miRNAs between control and high risk HCV patients was detected and found to possibly target genes related to HCC development and progression. The sensitivity and specificity of miR-618 for detecting HCC among HCV-positive individuals was found to be 64% and 68%, respectively. Whereas, the sensitivity and specificity of miR-650 were 72% and 58%, respectively. Additionally, the sensitivity and specificity for miR-618/650 in tandem were 58% and 75%, respectively. These predictive values are greatly improved compared to the traditional α-feto protein (AFP) level-based detection method. The proposed HCC miRNA signatures may therefore be of great value for the early diagnosis of HCC, before the onset of disease in HCV-positive patients. The significance of this approach is amplified by the use of urine as a sample source as it offers a non-invasive approach for developing screening methods that can reduce mortality rates.

摘要

微小RNA(miRNA)是内源性表达的小非编码RNA,它们在翻译水平上负向调节蛋白质编码基因的表达。越来越多的证据,如miRNA的异常表达,表明它们在癌症发展中发挥作用。它们已在各种肿瘤类型中被鉴定出来,这表明不同的miRNA组通常在不同的癌症中失调。为了鉴定丙型肝炎病毒(HCV)相关肝细胞癌(HCC)特有的miRNA特征,使用全基因组表达谱分析对32例HCV感染后的HCC患者、74例HCV阳性个体和12例对照个体进行了miRNA表达谱分析。检测到对照与高风险HCV患者之间两种个体miRNA的差异表达,并发现它们可能靶向与HCC发展和进展相关的基因。发现miR-618在HCV阳性个体中检测HCC的敏感性和特异性分别为64%和68%。而miR-650的敏感性和特异性分别为72%和58%。此外,miR-618/650串联检测的敏感性和特异性分别为58%和75%。与传统的基于甲胎蛋白(AFP)水平的检测方法相比,这些预测值有了很大提高。因此,所提出的HCC miRNA特征对于在HCV阳性患者疾病发作前早期诊断HCC可能具有重要价值。通过使用尿液作为样本来源,这种方法的意义得到了增强,因为它为开发可降低死亡率的筛查方法提供了一种非侵入性方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bd0/3245605/c3056612aa6b/jcav03p0019g01.jpg

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