黄曲霉毒素B1暴露的肝癌和肝硬化患者MicroRNA-24表达的研究

A. Attia, D. Elhammady, Maha R. Habeeb, N. Abbas, M. Zaki
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引用次数: 0

摘要

导语:超过80%的肝细胞癌(HCC)患者发生在发展中国家,是由于暴露于乙型或丙型肝炎病毒,通过乙肝病毒形成肝硬化或病毒整合到宿主DNA中,或由于摄入黄曲霉毒素B1 (AFB1)导致肝组织DNA损伤并产生突变,特别是p53肿瘤抑制基因。MicroRNAs是非编码rna,它影响癌基因和肿瘤抑制基因的表达,从而参与致癌作用。HCC与microrna表达失调之间的联系已被反复证实,这表明循环microrna可能潜在地被用作临床前HCC检测的生物标志物。我们在这项研究中旨在评估微核糖核酸-24 (microRNA-24)表达在经历高水平AFB1暴露的肝硬化和HCC患者中的作用。材料与方法:50例HCC患者和24例肝硬化患者,20例健康对照。采用酶联免疫吸附法(ELISA)检测黄曲霉毒素B1,实时聚合酶链反应(real-time PCR)检测microRNA-24。结果:与对照组相比,所有患者组的黄曲霉毒素B1水平和microRNA-24表达均显著增加,HCC组的黄曲霉毒素B1水平和microRNA-24表达明显高于肝硬化组(p小于0.0001)。与对照组相比,两组患者AFB1水平和microRNA-24表达量之间存在高度显著的相关性(p小于0.0001)。用于评估microRNA-24区分HCC和肝硬化能力的受试者工作特征(ROC)曲线显示,在截止点1.3时,其敏感性为80%,特异性为63%,具有高度显著性(p小于0.0001)。结论:在肝硬化和HCC患者中检测到的黄曲霉毒素B1水平升高进一步支持了先前评估埃及人群暴露于这种致癌物水平的研究,并支持黄曲霉毒素B1在HCC发生中的关键作用。此外,microRNA-24在肝硬化和HCC中的表达水平可能有价值,可作为HCC诊断的无创诊断工具。
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A Study of MicroRNA-24 Expression in Aflatoxin B1 Exposed Patients with Hepatocellular Carcinoma and Cirrhosis
Introduction: Over 80% of hepatocellular carcinoma (HCC) sufferers occur in developing countries as a result of exposure to hepatitis B or C viruses, through formation of cirrhosis or viral integration into host DNA on the part of HBV, or due to ingestion of aflatoxin B1 (AFB1) causing DNA damage in hepatic tissue with generation of mutations, particularly in p53 tumor suppressor gene. MicroRNAs are noncoding RNAs that have an effect on oncogene and tumor suppressor gene expression, hence partaking in carcinogenesis. A connection between HCC and dysregulated expression of microRNAs has been repeatedly demonstrated, suggesting that circulating microRNAs might potentially be used as biomarkers for pre-clinical HCC detection. We aimed in this study to assess the role of micro-ribonucleic acid-24 (microRNA-24) expression in patients with cirrhosis and HCC who have experienced high levels of AFB1 exposure.Materials and Methods: Fifty HCC and 24 hepatic cirrhosis patients, in addition to 20 healthy control subjects were included in this study. Aflatoxin B1 was measured by enzyme-linked immunosorbent assay (ELISA) and microRNA-24 was detected using real-time polymerase chain reaction (real-time PCR).Results: Both aflatoxin B1 levels and microRNA-24 expression were found to be significantly increased in all patient groups in comparison to controls, more so in the HCC than cirrhotic group (p˂0.0001). A highly significant correlation was detected between levels of AFB1 and amount of microRNA-24 expressed in both patient groups relative to their control counterparts (p˂0.0001). Receiver Operating Characteristic (ROC) curve performed to evaluate the ability of microRNA-24 to differentiate between HCC and cirrhosis showed that it had sensitivity of 80% and specificity of 63% at cutoff 1.3, which was highly significant (p˂0.0001).Conclusion: Increased aflatoxin B1 levels detected in patients with cirrhosis and HCC further support previous studies evaluating the level of exposure of the Egyptian population to this carcinogen and support the critical role of aflatoxin B1 in the appearance of HCC. In addition, microRNA-24 expression levels demonstrated in both cirrhosis and HCC might be valuable for use as a noninvasive diagnostic tool for diagnosis of HCC.
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