Guo Xin, Lv Xiaohui, Lv Xing, Ma Yueyun, Chen Lin, Chen Yong
Department of General Surgery, Chinese PLA General Hospital, Beijing, P.R. China.
Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
Oncotarget. 2017 Jul 4;8(27):44050-44058. doi: 10.18632/oncotarget.17211.
Serum miRNAs have gained great popularity to act as circulating biomarkers of several cancers. In this study, we aimed to evaluate the diagnostic efficiency of serum miR-21 as novel biomarkers for patients with hepatocellular carcinoma (HCC) and other controls. A total of 533 individuals were recruited and conducted in a two-step analysis. The pilot group included 40 HCC patients and 40 healthy donors. The expression levels of miR-21 were significantly higher in primary HCC tissues than in adjacent noncancerous tissues (P<0.0001). HCC patients exhibited significantly higher serum levels of miR-21 than HD (P<0.0001). In the verification group, the mean serum levels of miR-21 in 175 patients with HCC were significantly higher than in 64 with CHB, 78 with LC and 136 HD (all P<0.0001). ROC curves demonstrated that the AUC of miR-21 was 0.849, sensitivity 82.1% and specificity 83.9%. Furthermore, serum miR-21 maintained its diagnostic efficiency in AFP-negative HCC subgroups with AUC 0.831, sensitivity 81.2% and specificity 83.2%. The serum levels of miR-21 could distinguish HCC from CHB and LC (AUC 0.789, sensitivity 76.9%, specificity 85.7% and AUC 0.814, sensitivity 80.8%, specificity 72.9%, respectively). In addition, the serum levels of miR-21 were significantly associated with clinical stage (P=0.006) and distant metastasis (P=0.000). Thus, our findings suggest that miR-21 together with AFP may help enhance the diagnosis of HCC, especially of AFP-negative HCC, and could distinguish HCC from CHB and LC.
血清微小RNA（miRNA）作为多种癌症的循环生物标志物已广受欢迎。在本研究中，我们旨在评估血清miR-21作为肝细胞癌（HCC）患者及其他对照的新型生物标志物的诊断效能。共招募了533名个体并进行了两步分析。试点组包括40例HCC患者和40名健康供体。miR-21在原发性HCC组织中的表达水平显著高于相邻的非癌组织（P<0.0001）。HCC患者血清miR-21水平显著高于健康供体（P<0.0001）。在验证组中，175例HCC患者的血清miR-21平均水平显著高于64例慢性乙型肝炎（CHB）患者、78例肝硬化（LC）患者和136名健康供体（均P<0.0001）。ROC曲线显示，miR-21的曲线下面积（AUC）为0.849，敏感性为 82.1%，特异性为83.9%。此外，血清miR-21在甲胎蛋白（AFP）阴性的HCC亚组中保持其诊断效能，AUC为0.831，敏感性为81.2%，特异性为83.2%。血清miR-21水平可将HCC与CHB和LC区分开来（AUC分别为0.789，敏感性为76.9%，特异性为85.7%；以及AUC为0.814，敏感性为80.8%，特异性为72.9%）。此外，血清miR-21水平与临床分期（P=0.006）和远处转移（P=0.000）显著相关。因此，我们的研究结果表明，miR-21与AFP一起可能有助于提高HCC的诊断，尤其是AFP阴性的HCC，并可将HCC与CHB和LC区分开来。
