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血清miRNA-101表达特征作为埃及患者丙型肝炎病毒相关肝细胞癌的非侵入性诊断生物标志物。

Serum miRNA-101 expression signature as non-invasive diagnostic biomarker for Hepatitis C virus-associated hepatocellular carcinoma in Egyptian patients.

作者信息

Sharafeldin Mostafa A, Suef Reda A, Mousa Adel A, Ziada Dina H, Farag Mohamed M S

机构信息

Botany and Microbiology Department, Faculty of Science, Al-Azhar University, Cairo, 11884, Egypt.

Department of Tropical Medicine and Infectious Diseases, Faculty of Medicine, Tanta University, Tanta, Egypt.

出版信息

Sci Rep. 2025 Jan 3;15(1):645. doi: 10.1038/s41598-024-81207-2.

Abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality globally due to HCC late diagnosis and limited treatment options. MiRNAs (miRNAs) emerged as potential biomarkers for various diseases, including HCC. However, the value of miRNA-101 as a serum biomarker for HCV-induced HCC has not been fully investigated. Our study aims to investigate the miRNA-101 differential expression in Egyptian HCV-induced HCC patients' serum versus HCV liver cirrhosis (LC) as prospective diagnostic biomarkers compared to alpha-fetoprotein (AFP). Blood samples were collected for clinical chemistry profile, liver function, and serum AFP investigations. The serum miR-101 expression levels were evaluated using real-time quantitative PCR (RT-qPCR) in 100 Egyptian subjects: 40 HCV-induced HCC, 40 HCV-induced cirrhosis, and 20 healthy controls. HCC patients showed significantly higher TB, DB, and AFP levels than those cirrhosis and control groups, whereas ALB and Total Protein exhibited significantly reduced levels. AFP sensitivity and specificity in differentiating HCC reported 60 and 67%, respectively, at the cut-off values of 7ng/dl. miR-101 shows fold change upregulation in HCC patients (P < 0.0001) compared to LC and control groups. ROC curve demonstrated miR-101 (AUC) of 0.9556, sensitivity 92.5%, and specificity 97.5%, highlighting the miR-101 diagnostic potential as a biomarker for HCC detection. Elevated miR-101 levels in HCC are significantly correlated with a higher number and larger size of focal lesions, advanced BCLC staging, and Child-Pugh score. These findings highlight the utility of miR-101 as a predictive and diagnostic non-invasive biomarker for HCV-related HCC from cirrhotic populations. More research is warranted to validate the clinical validity of miR-101 and explore underlying mechanisms in HCV-HCC progression.

摘要

由于肝细胞癌(HCC)诊断较晚且治疗选择有限,它是全球癌症死亡的主要原因。微小RNA(miRNA)已成为包括HCC在内的各种疾病的潜在生物标志物。然而,miRNA-101作为丙型肝炎病毒(HCV)诱导的HCC血清生物标志物的价值尚未得到充分研究。我们的研究旨在调查埃及HCV诱导的HCC患者血清中miRNA-101与HCV肝硬化(LC)相比的差异表达,作为与甲胎蛋白(AFP)相比的前瞻性诊断生物标志物。采集血样进行临床化学分析、肝功能检查和血清AFP检测。使用实时定量聚合酶链反应(RT-qPCR)评估100名埃及受试者血清中miR-101的表达水平:40例HCV诱导的HCC患者、40例HCV诱导的肝硬化患者和20名健康对照者。HCC患者的总胆红素(TB)、直接胆红素(DB)和AFP水平显著高于肝硬化组和对照组,而白蛋白(ALB)和总蛋白水平显著降低。在7ng/dl的临界值时,AFP区分HCC的敏感性和特异性分别为60%和67%。与LC组和对照组相比,HCC患者中miR-101显示上调倍数变化(P < 0.0001)。ROC曲线显示miR-101的曲线下面积(AUC)为0.9556,敏感性为92.5%,特异性为97.5%,突出了miR-101作为HCC检测生物标志物的诊断潜力。HCC中miR-101水平升高与局灶性病变数量增多、体积增大、BCLC分期进展和Child-Pugh评分显著相关。这些发现突出了miR-101作为肝硬化人群中HCV相关HCC的预测和诊断非侵入性生物标志物的效用。有必要进行更多研究以验证miR-101的临床有效性,并探索HCV-HCC进展的潜在机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ef7/11698908/410f7af23f1a/41598_2024_81207_Fig1_HTML.jpg

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