Farrokhi Yekta Reyhaneh, Rezaei Tavirani Mostafa, Arefi Oskouie Afsaneh, Amiri-Dashatan Nasrin
Proteomics Research Center, School of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Basic Sciences, School of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Asian Pac J Cancer Prev. 2025 Jan 1;26(1):249-262. doi: 10.31557/APJCP.2025.26.1.249.
Hepatocellular carcinoma (HCC), the most common form of liver cancer, has a significant mortality rate, largely due to late diagnosis. Recent advances in medical research have demonstrated the potential of biomarkers for early detection. Moreover, the discovery and use of prognostic biomarkers offer a ray of hope in the fight against liver cancer.
Three gene transcript collections (GSE57957, GSE76427, and GSE84402) were retrieved from the GEO database, and significantly expressed genes were identified through a comprehensive screening process. Subsequently, key potential biomarkers were identified using various methods, including functional pathway enrichment, protein-protein interaction network analysis, mRNA-miR interaction study, and ROC curve and survival analysis.
After analyzing the expression of hub proteins and miRs, 12 proteins were found to have AUC values greater than 0.9 and log-rank KM-plot p values less than 0.05. Therefore, these proteins can be considered as potential diagnostic and prognostic biomarkers. Among these proteins, the top 5 were CDC6, PTTG1, CDCA5, RACGAP1, and RAD51AP1. The microRNAs with the highest diagnostic significance (AUC≥0.8) were hsa-mir-101-3p, hsa-mir-195-5p, hsa-mir-130a-3p, hsa-mir-26b-5p, hsa-mir-29c-3p, hsa-mir-26a-5p, and hsa-mir-34a-5p. Notably, hsa-mir-34a-5p, hsa-mir-195-5p, and hsa-mir-130a-3p also showed prognostic potential as predictors of overall survival in HCC patients.
Harnessing the potential of these biomarkers will enable healthcare professionals to make informed decisions, leading to improved care and more favorable outcomes in the fight against HCC. However, the next step is to thoroughly validate these potential markers in large cohorts.
肝细胞癌(HCC)是最常见的肝癌形式,死亡率很高,主要原因是诊断较晚。医学研究的最新进展已证明生物标志物在早期检测方面的潜力。此外,预后生物标志物的发现和应用为抗击肝癌带来了一线希望。
从基因表达综合数据库(GEO数据库)中检索了三个基因转录本集合(GSE57957、GSE76427和GSE84402),并通过全面筛选过程鉴定出显著表达的基因。随后,使用多种方法鉴定关键潜在生物标志物,包括功能通路富集、蛋白质-蛋白质相互作用网络分析、mRNA-微小RNA(miR)相互作用研究以及受试者工作特征(ROC)曲线和生存分析。
在分析核心蛋白和微小RNA的表达后,发现12种蛋白的曲线下面积(AUC)值大于0.9且对数秩Kaplan-Meier曲线(KM-plot)p值小于0.05。因此,这些蛋白可被视为潜在的诊断和预后生物标志物。在这些蛋白中,排名前5的是细胞分裂周期蛋白6(CDC6)、垂体肿瘤转化基因1(PTTG1)、细胞分裂周期相关蛋白5(CDCA5)、RACGTP酶激活蛋白1(RACGAP1)和RAD51相关蛋白1(RAD51AP1)。具有最高诊断意义(AUC≥0.8)的微小RNA是hsa-mir-101-3p、hsa-mir-195-5p、hsa-mir-130a-3p、hsa-mir-26b-5p、hsa-mir-29c-3p、hsa-mir-26a-5p和hsa-mir-34a-5p。值得注意的是,hsa-mir-34a-5p、hsa-mir-195-5p和hsa-mir-130a-3p作为HCC患者总生存的预测指标也显示出预后潜力。
利用这些生物标志物的潜力将使医疗保健专业人员能够做出明智的决策,从而在抗击HCC方面改善护理并取得更有利的结果。然而,下一步是在大型队列中彻底验证这些潜在标志物。