Zhao Qi, Sun Xiangfei, Liu Chao, Li Tao, Cui Juan, Qin Chengyong
Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
Department of Cardiovasular Surgery, Qilu Hospital of Shandong University, Qingdao, Shandong 266035, P.R. China.
Oncol Lett. 2018 May;15(5):6115-6122. doi: 10.3892/ol.2018.8117. Epub 2018 Feb 26.
The aims of the present study were to identify the expression profile of microRNA (miR)-143/145 in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC), explore its association with prognosis and investigate whether the serum miR-143/145 expression levels may serve as a diagnostic indicator of HBV-associated HCC. The microRNA (miRNA) chromatin immunoprecipitation dataset was obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus databases, and analyzed using the Wilcoxon signed-rank test. It was observed that the expression of miR-143 and miR-145 was decreased 1.5-fold in HBV-associated HCC samples compared with non-tumor tissue in the TCGA and the GSE22058 datasets (P<0.01). Using the reverse transcription-quantitative polymerase chain reaction, it was further confirmed that miR-143/145 and their host gene MIR143HG were downregulated in HBV-associated HCC tissues compared with corresponding distal non-tumor tissues. The lower level of miR-143 and miR-145 expression was associated with tumor differentiation, and may thus be responsible for a poor prognosis of patients with HBV-associated HCC. The receiver-operating characteristic (ROC) curves were used to explore the potential value of miR-143 and miR-145 as biomarkers for predicting HBV-associated HCC tumorigenesis. In serum, miR-143/145 were identified to be significantly decreased in patients with HBV-associated HCC compared with negative control patients, and their associated areas under the ROC curves were calculated at 0.813 and 0.852 (P<0.05), with each having a sensitivity and a specificity close to 0.80. These results indicated that the decreased expression of the miR-143/145 cluster and their host gene MIR143HG in HBV-associated HCC tissue was associated with prognosis, and each of these miRNAs may serve as a valuable diagnostic biomarker for predicting HBV-associated HCC tumorigenesis.
本研究的目的是确定微小RNA(miR)-143/145在乙型肝炎病毒(HBV)相关肝细胞癌(HCC)中的表达谱,探讨其与预后的关系,并研究血清miR-143/145表达水平是否可作为HBV相关HCC的诊断指标。从癌症基因组图谱(TCGA)和基因表达综合数据库中获取微小RNA(miRNA)染色质免疫沉淀数据集,并使用Wilcoxon符号秩检验进行分析。结果发现,在TCGA和GSE22058数据集中,与非肿瘤组织相比,HBV相关HCC样本中miR-143和miR-145的表达降低了1.5倍(P<0.01)。通过逆转录定量聚合酶链反应进一步证实,与相应的远端非肿瘤组织相比,HBV相关HCC组织中miR-143/145及其宿主基因MIR143HG表达下调。miR-143和miR-145表达水平较低与肿瘤分化相关,因此可能是HBV相关HCC患者预后不良的原因。采用受试者工作特征(ROC)曲线探讨miR-143和miR-145作为预测HBV相关HCC发生生物标志物的潜在价值。在血清中,与阴性对照患者相比,HBV相关HCC患者的miR-143/145显著降低,其ROC曲线下面积分别为0.813和0.852(P<0.05),敏感性和特异性均接近0.80。这些结果表明,miR-143/145簇及其宿主基因MIR143HG在HBV相关HCC组织中的表达降低与预后相关,且每种miRNA均可作为预测HBV相关HCC发生的有价值诊断生物标志物。