Bio-diagnostic performances of microRNAs set related to DNA damage response pathway among hepatitis C virus-associated hepatocellular carcinoma patients.

IF 3.6 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Sara M Abdo, Wafaa Gh Shousha, Amal Ahmed Mohamed, Mohamed Elshobaky, Mohamed Saleh, Mostafa Mohamed Abdelhamid Ali
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Abstract

Background: Up to date, a well-defined microRNAs (miRNAs) profile involved in hepatocellular carcinoma (HCC) pathogenesis remains indecisive. Thus, employing miRNAs for HCC diagnosis is demanded for early therapeutic interventions. We aimed to evaluate the usage of miRNAs set related to the SuperPath: miRNAs involved in DNA damage response pathway as effective biomarkers for HCV-related HCC diagnosis.

Results: The study enrolled 97 patients with HCV-related HCC, 84 with hepatitis C virus (HCV), 97 with liver cirrhosis (LC), and 84 healthy individuals. Serum miRNA-23a, miRNA-203, miRNA-100-5p, and miRNA-16 were quantified using qRT-PCR experiments, AFP and routine LFTs were estimated via standard techniques. Pathway enrichment analysis along with the construction of miRNAs regulatory network were performed. With respect to healthy individuals, miRNA-203, miRNA-100-5p, and miRNA-16 were significantly downregulated in HCC, HCV, and LC groups, while miRNA-23a showed significant upregulation (p < 0.001). miRNAs exhibited significant correlations with AFP, ALT, AST, and albumin. Also, elevated levels of miRNA-23a were recognized in patients with multiple focal lesions and/or lesion size > 5 cm. Additionally, the diagnostic performance of miRNA-23a expression level at a selected cut-off value of 3.99 overtakes AFP, while expressions of miR-203, miRNA-100-5p, and miRNA-16 represent poor diagnostic outcomes.

Conclusions: Keeping in mind the individual variability and high level of heterogeneity in HCC, our data revealed the diagnostic value of miRNA-23a expression in HCV-related HCC patients. Further extra in silico HCC-specific microRNAs sets are demanded in diagnosis.

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与DNA损伤反应通路相关的microrna在丙型肝炎病毒相关性肝癌患者中的生物诊断价值
背景:迄今为止,参与肝细胞癌(HCC)发病机制的明确的microRNAs (miRNAs)谱仍未确定。因此,早期治疗干预需要使用mirna进行HCC诊断。我们的目的是评估与SuperPath相关的miRNAs:参与DNA损伤反应途径的miRNAs作为hcv相关HCC诊断的有效生物标志物的使用情况。结果:该研究纳入了97例HCV相关HCC患者,84例丙型肝炎病毒(HCV)患者,97例肝硬化(LC)患者和84名健康个体。采用qRT-PCR实验定量血清miRNA-23a、miRNA-203、miRNA-100-5p和miRNA-16,采用标准技术估计AFP和常规lft。途径富集分析和miRNAs调控网络构建。相对于健康个体,miRNA-203、miRNA-100-5p和miRNA-16在HCC、HCV和LC组中显著下调,而miRNA-23a显著上调(p 5 cm)。此外,在选定的临界值3.99处,miRNA-23a表达水平的诊断性能超过AFP,而miR-203、miRNA-100-5p和miRNA-16的表达则代表较差的诊断结果。结论:考虑到HCC的个体差异和高度异质性,我们的数据揭示了miRNA-23a表达在hcv相关HCC患者中的诊断价值。在诊断中需要进一步额外的硅hcc特异性microrna集。
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