Department of Biochemistry and Genome Biology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Int J Exp Pathol. 2022 Dec;103(6):245-251. doi: 10.1111/iep.12457. Epub 2022 Sep 24.
Hepatocellular carcinoma (HCC) is the most predominant type of liver cancer and is frequently fatal. Alpha-fetoprotein, alpha-fetoprotein-L3, and protein induced by vitamin K absence or antagonist-II are used as biomarkers to diagnose HCC. However, these biomarkers are not highly specific, especially for early-stage HCC diagnosis; therefore, more specific biomarkers are needed. Recently, circular RNA (circRNA) biomarkers have been used to diagnose several intractable diseases. In this study, we sought to identify circRNA biomarkers for the specific diagnosis of HCC. To this end, we compared the expression levels of circRNAs in primary HCC and normal tissues using publicly available RNA-seq data. Our analysis revealed that the expression levels of eight circRNAs were altered in primary HCC tissues compared with normal tissues. To confirm our findings, we examined the expression levels of selected circRNAs in HCC cell lines and normal hepatocytes. The expression level of hsa_circ_0001438, a circRNA that was downregulated in primary HCC, was lower in poorly and well-differentiated HCC cell lines than in normal hepatocytes. By contrast, the expression level of hsa_circ_0000417, which was increased in primary HCC, was strongly upregulated in a well-differentiated HCC cell line compared with normal hepatocytes. Thus, hsa_circ_0001438 and hsa_circ_0000417 might be potential biomarkers for the specific diagnosis of HCC. The experimental strategy described here, using publicly available RNA-seq data, is a useful and cost-effective method of identifying circRNA biomarkers.
肝细胞癌（HCC）是最主要的肝癌类型，经常致命。甲胎蛋白、甲胎蛋白-L3 和维生素 K 缺乏或拮抗剂-II 诱导蛋白被用作诊断 HCC 的生物标志物。然而，这些生物标志物的特异性不高，特别是对于早期 HCC 的诊断；因此，需要更具特异性的生物标志物。最近，环状 RNA（circRNA）生物标志物已被用于诊断几种难治性疾病。在这项研究中，我们试图确定用于 HCC 特异性诊断的 circRNA 生物标志物。为此，我们使用公开的 RNA-seq 数据比较了原发性 HCC 和正常组织中 circRNA 的表达水平。我们的分析表明，与正常组织相比，原发性 HCC 组织中 8 种 circRNA 的表达水平发生了改变。为了验证我们的发现，我们检测了 HCC 细胞系和正常肝细胞中选定 circRNA 的表达水平。在原发性 HCC 中下调的 hsa_circ_0001438 的表达水平在分化不良和分化良好的 HCC 细胞系中低于正常肝细胞。相比之下，在原发性 HCC 中上调的 hsa_circ_0000417 的表达水平在分化良好的 HCC 细胞系中与正常肝细胞相比强烈上调。因此，hsa_circ_0001438 和 hsa_circ_0000417 可能是 HCC 特异性诊断的潜在生物标志物。这里描述的使用公开 RNA-seq 数据的实验策略是识别 circRNA 生物标志物的一种有用且具有成本效益的方法。
