Fu Liyun, Wu Shengdong, Yao Ting, Chen Qingqing, Xie Yi, Ying Sheng, Chen Zhigang, Xiao Bingxiu, Hu Yaoren
Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, China.
Department of Hepatology, Ningbo No. 2 Hospital and the Affiliated Hospital, Medical School of Ningbo University, Ningbo, China.
J Clin Lab Anal. 2018 Feb;32(2). doi: 10.1002/jcla.22239. Epub 2017 May 11.
Circular RNAs (circRNAs) constitute a class of non-coding RNAs recently discovered to be widespread and abundant in mammalian cells. However, the expression features of most of circRNAs in hepatocellular carcinoma (HCC) are unraveled. In this study, we focused on hsa_circ_0003570, which was found to be down-regulated in HCC tissues in our previous microarray screening.
The hsa_circ_0003570 levels in HCC cell lines, HepG2, SMMC-7721, MHCC97L, MHCC97H, and HCCLM3, and human normal hepatic cell line L02 were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Then, its levels in 107 paired HCC tissues and adjacent non-tumor tissues, 60 liver biopsy samples from patients with chronic liver diseases were detected by qRT-PCR. The receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of hsa_circ_0003570 for HCC.
Hsa_circ_0003570 was not only first found down-regulated in HCC cell lines (P<.001) but also in HCC tissues (P<.001). Moreover, hsa_circ_0003570 was gradually decreased from chronic hepatitis (CH), to liver cirrhosis (LC) and to HCC tissues (P<.01). Its expression levels were significantly correlated with tumor diameter (P=.035), differentiation (P=.013), microvascular invasion (P=.045), Barcelona Clinic Liver Cancer stages (P=.011), tumor-node-metastasis stages (P=.016), and serum alpha-fetoprotein levels (P=.031). The ROC curve demonstrated that hsa_circ_0003570 had poor performance for differentiating HCC from LC and CH, but had relatively good performance for differentiating LC from CH.
These results indicated that hsa_circ_0003570 expression levels were associated with HCC clinicopathological characteristics.
环状RNA（circRNAs）是一类最近发现的在哺乳动物细胞中广泛且丰富存在的非编码RNA。然而，大多数circRNAs在肝细胞癌（HCC）中的表达特征仍未阐明。在本研究中，我们聚焦于hsa_circ_0003570，在我们之前的微阵列筛选中发现其在HCC组织中表达下调。
采用定量逆转录-聚合酶链反应（qRT-PCR）检测HCC细胞系HepG2、SMMC-7721、MHCC97L、MHCC97H和HCCLM3以及人正常肝细胞系L02中hsa_circ_0003570的水平。然后，用qRT-PCR检测107对HCC组织及癌旁非肿瘤组织、60例慢性肝病患者肝活检样本中hsa_circ_0003570的水平。采用受试者工作特征曲线（ROC）评估hsa_circ_0003570对HCC的诊断价值。
不仅首次发现hsa_circ_0003570在HCC细胞系中表达下调（P<0.001），在HCC组织中也是如此（P<0.001）。此外，hsa_circ_0003570从慢性肝炎（CH）、肝硬化（LC）到HCC组织逐渐降低（P<0.01）。其表达水平与肿瘤直径（P=0.035）、分化程度（P=0.013）、微血管侵犯（P=0.045）、巴塞罗那临床肝癌分期（P=0.011）、肿瘤-淋巴结-转移分期（P=0.016）及血清甲胎蛋白水平（P=0.031）显著相关。ROC曲线显示，hsa_circ_0003570在区分HCC与LC及CH方面性能不佳，但在区分LC与CH方面性能相对较好。
这些结果表明hsa_circ_0003570表达水平与HCC临床病理特征相关。
