Moshiri Farzaneh, Salvi Alessandro, Gramantieri Laura, Sangiovanni Angelo, Guerriero Paola, De Petro Giuseppina, Bassi Cristian, Lupini Laura, Sattari Arash, Cheung Douglas, Veneziano Dario, Nigita Giovanni, Shankaraiah Ram C, Portolani Nazario, Carcoforo Paolo, Fornari Francesca, Bolondi Luigi, Frassoldati Antonio, Sabbioni Silvia, Colombo Massimo, Croce Carlo M, Negrini Massimo
Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.
Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA.
Oncotarget. 2018 Feb 27;9(20):15350-15364. doi: 10.18632/oncotarget.24601. eCollection 2018 Mar 16.
Hepatocellular carcinoma (HCC) is the most common liver cancer and second leading cause of cancer related death worldwide. Most HCCs occur in a damaged cirrhotic background and it may be difficult to discriminate between regenerative nodules and early HCCs. No dependable molecular biomarker exists for the early detection of HCC. MicroRNAs (miRNAs) have attracted attention as potential blood-based biomarkers. To identify circulating miRNAs with diagnostic potential in HCC, we performed preliminary RNAseq studies on plasma samples from a small set of HCC patients, cirrhotic patients and healthy controls. Then, out of the identified miRNAs, we investigated miR-101-3p, miR-106b-3p, miR-1246 and miR-411-5p in plasma of independent HCC patients' cohorts. The use of droplet digital PCR (ddPCR) confirmed the aberrant levels of these miRNAs. The diagnostic performances of each miRNA and their combinations were measured using Receiver Operating Characteristic (ROC) curve analyses: a classifier consisting of miR-101-3p, miR-1246 and miR-106b-3p produced the best diagnostic precision in plasma of HCC vs. cirrhotic patients (AUC = 0.99). A similar performance was found when the levels of miRNAs of HCC patients were compared to healthy controls (AUC = 1.00). We extended the analyses of the same miRNAs to serum samples. In serum of HCC vs. cirrhotic patients, the combination of miR-101-3p and miR-106b-3p exhibited the best diagnostic accuracy with an AUC = 0.96. Thus, circulating miR-101-3p, miR-106b-3p and miR-1246, either individually or in combination, exhibit a considerable potential value as diagnostic biomarkers of HCC.
肝细胞癌（HCC）是最常见的肝癌，也是全球癌症相关死亡的第二大主要原因。大多数HCC发生在受损的肝硬化背景下，可能难以区分再生结节和早期HCC。目前尚无可靠的分子生物标志物用于HCC的早期检测。微小RNA（miRNA）作为潜在的血液生物标志物受到关注。为了鉴定具有HCC诊断潜力的循环miRNA，我们对一小部分HCC患者、肝硬化患者和健康对照的血浆样本进行了初步的RNA测序研究。然后，在鉴定出的miRNA中，我们在独立的HCC患者队列血浆中研究了miR-101-3p、miR-106b-3p、miR-1246和miR-411-5p。使用液滴数字PCR（ddPCR）证实了这些miRNA的异常水平。使用受试者工作特征（ROC）曲线分析测量每个miRNA及其组合的诊断性能：由miR-101-3p、miR-1246和miR-106b-3p组成的分类器在HCC与肝硬化患者血浆中产生了最佳诊断精度（AUC = 0.99）。当将HCC患者的miRNA水平与健康对照进行比较时，发现了类似的性能（AUC = 1.00）。我们将相同miRNA的分析扩展到血清样本。在HCC与肝硬化患者的血清中，miR-101-3p和miR-106b-3p的组合表现出最佳诊断准确性，AUC = 0.96。因此，循环miR-101-3p、miR-106b-3p和miR-1246，单独或联合使用，作为HCC的诊断生物标志物具有相当大的潜在价值。
