Jang Jeong Won, Kim Ji Min, Kim Hye Seon, Kim Jin Seoub, Han Ji Won, Lee Soon Kyu, Nam Heechul, Sung Pil Soo, Bae Si Hyun, Choi Jong Young, Yoon Seung Kew
Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea.
The Catholic University Liver Research Center, The Catholic University of Korea, Seoul, Korea.
J Liver Cancer. 2022 Mar;22(1):30-39. doi: 10.17998/jlc.2022.02.25. Epub 2022 Mar 21.
BACKGROUND/AIM: Hepatocellular carcinoma (HCC) is associated with poor prognosis, largely due to late detection. Highly accurate biomarkers are urgently needed to detect early-stage HCC. Our study aims to explore the diagnostic performance of serum exosomal microRNA (miR)-720 in HCC.
Exosomal miRNA was measured via quantitative real-time PCR. A correlation analysis of exosomal miR-720 and tumor or clinico-demographic data of patients with HCC was performed. The receiver operating characteristic (ROC) curve was used to assess the diagnostic capacity of serum exosomal miR-720 for HCC, in comparison with α-fetoprotein (AFP) and prothrombin induced by vitamin K absence or antagonist-II (PIVKA-II).
MiR-720 was chosen as a potential HCC marker via miR microarray based on significant differential expression between tumor and non-tumor samples. Serum exosomal miR-720 was significantly upregulated in patients with HCC (n=114) versus other liver diseases (control, n=30), with a higher area under the ROC curve (AUC, 0.931) than the other markers. Particularly, serum exosomal miR-720 showed superior performance in diagnosing small HCC (<5 cm; AUC, 0.930) compared with AFP (AUC, 0.802) or PIVKA-II (AUC, 0.718). Exosomal miR-720 levels showed marginal correlation with tumor size. The proportion of elevated miR-720 also increased with intrahepatic tumor stage progression. Unlike AFP or PIVKA-II showing a significant correlation with aminotransferase levels, the exosomal miR-720 level was not affected by aminotransferase levels.
Serum exosomal miR-720 is an excellent biomarker for the diagnosis of HCC, with better performance than AFP or PIVKA-II. Its diagnostic utility is maintained even in small HCC and is unaffected by aminotransferase levels.
背景/目的：肝细胞癌（HCC）的预后较差，主要原因是发现较晚。迫切需要高度准确的生物标志物来检测早期HCC。本研究旨在探讨血清外泌体微小RNA（miR）-720在HCC中的诊断效能。
通过定量实时PCR检测外泌体miRNA。对HCC患者的外泌体miR-720与肿瘤或临床人口统计学数据进行相关性分析。与甲胎蛋白（AFP）和维生素K缺乏或拮抗剂-II诱导的凝血酶原（PIVKA-II）相比，采用受试者操作特征（ROC）曲线评估血清外泌体miR-720对HCC的诊断能力。
基于肿瘤与非肿瘤样本之间的显著差异表达，通过miR芯片将miR-720选为潜在的HCC标志物。与其他肝病（对照组，n = 30）相比，HCC患者（n = 114）血清外泌体miR-720显著上调，其ROC曲线下面积（AUC，0.931）高于其他标志物。特别是，与AFP（AUC，0.802）或PIVKA-II（AUC，0.718）相比，血清外泌体miR-720在诊断小肝癌（<5 cm；AUC，0.930）方面表现更优。外泌体miR-720水平与肿瘤大小呈微弱相关性。随着肝内肿瘤分期进展，miR-720升高的比例也增加。与AFP或PIVKA-II与转氨酶水平显著相关不同，外泌体miR-720水平不受转氨酶水平影响。
血清外泌体miR-720是诊断HCC的优秀生物标志物，性能优于AFP或PIVKA-II。即使在小肝癌中其诊断效用也能保持，且不受转氨酶水平影响。
