肝癌患者外周血单个核细胞circRNAs诊断价值分析

Diagnostic value of circular RNAs in peripheral blood mononuclear cells in hepatocellular carcinoma patients

目的探讨肝细胞癌(HCC)患者外周血单个核细胞(PBMCs)中环状RNA(circRNAs)作为HCC分子标志物的临床诊断价值。方法利用高通量测序(RNA-seq)获取4例HCC患者和3例健康对照者(NC组)PBMCs中circRNAs的差异表达谱,GO/KEGG分析差异表达的circRNAs显著富集的潜在功能和信号通路;qRT-PCR对其中6种显著差异的circRNAs在72例HCC患者和30例健康对照者PBMCs样本中再次验证;最后结合ROC曲线(ROC)评估circ0000798作为HCC分子诊断标志物的潜力。结果RNA-seq鉴定出HCC组较NC组共有58种显著差异的circRNAs(21种上调,37种下调);GO/KEGG分析发现差异表达的circRNAs多涉及免疫和免疫相关的信号通路;qRT-PCR结果表明circ0000798在HCC患者PBMCs中表达显著高于NC组(P<0.05),ROC曲线分析提示circ0000798有潜力作为HCC分子诊断标志物。结论HCC患者PBMCs中显著差异表达的circ0000798有潜力作为HCC患者无创性诊断分子标志物。

CircRNA is a novel class of non-coding RNA and involved in the occurrence of many diseases,especially in cancer. Therefore, high throughput sequencing(RNA-seq) was used to obtain the differential expression profile of circRNAs between HCC group and normal control group(NC) in this study and to detect the differentially expressed circRNAs, and further bioinformatics analysis was performed to predict its potential function. The selected six circRNAs were further confirmed by qRT-PCR in 102 PBMCs samples and the value of circ0000798 in diagnosing HCC was explored. Data showed there are 58 markedly dysregulated circRNAs between HCC group and NC group, including 21 upregulated and 37 downregulated circRNAs, and bioinformatics analysis revealed that the differentially expressed circRNAs are mostly involved in immune or immune-related signaling pathways. The 6 selected dysregulated circRNAs were confirmed to be consistent with the RNA-seq, and the receiver operating characteristic(ROC) curve indicated the potential diagnostic value of circ0000798 for HCC. Our results identified that the aberrant circ0000798 can be used as a diagnostic marker for HCC patients.