Circulating microRNAs as Potential Diagnostic and Prognostic Biomarkers in Hepatocellular Carcinoma
Circulating microRNAs as Potential Diagnostic and Prognostic Biomarkers in Hepatocellular Carcinoma
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DOI：
10.1038/s41598-019-46872-8
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发表时间：
2019-07-18
影响因子：
4.6
通讯作者：
Lee, Caroline G. L.
中科院分区：
文献类型：
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作者：
Jin, Yu;Wong, Ye Shen;Lee, Caroline G. L.
肝细胞癌（HCC）是第五大常见癌症，由于诊断较晚和治疗方案有限，死亡率高。血液mirna以高度稳定的无细胞形式循环，有望成为早期检测HCC的新型潜在生物标志物。在HCC和正常健康（NH）志愿者之间进行全miRNome分析，以确定失调的mirna。这些失调的miRNA在HCC、NH和慢性乙型肝炎（CHB）志愿者的独立队列中得到验证，最后在由NH、CHB、肝硬化和HCC志愿者组成的第三个队列中得到验证，以评估疾病进展过程中miRNA的变化。分析循环mirna与肝损伤标志物、临床病理特征和生存结果之间的关系，以确定预后标志物。在所有三个队列中，HCC和NH个体之间有12种mirna的差异表达。在CHB、肝硬化和HCC患者中，五种上调的mirna （miR-122-5p、miR-125b-5p、miR-885-5p、miR-100-5p和miR-148a-3p）是CHB感染的潜在生物标志物，而miR-34a-5p可能是肝硬化的生物标志物。值得注意的是，四种mirna （miR-1972, miR-193a-5p， miR-214-3p和miR-365a-3p）可以区分HCC和其他非HCC个体。6种mirna是总生存期的潜在预后标志物。
Hepatocellular carcinoma (HCC) is the fifth most common cancer with high mortality, due to late diagnosis and limited treatment options. Blood miRNAs, which circulate in a highly stable, cell-free form, show promise as novel potential biomarkers for early detection of HCC. Whole miRNome profiling was performed to identify deregulated miRNAs between HCC and normal healthy (NH) volunteers. These deregulated miRNAs were validated in an independent cohort of HCC, NH and chronic Hepatitis B (CHB) volunteers and finally in a 3rd cohort comprising NH, CHB, cirrhotic and HCC volunteers to evaluate miRNA changes during disease progression. The associations between circulating miRNAs and liver-damage markers, clinicopathological characteristics and survival outcomes were analysed to identify prognostic markers. Twelve miRNAs are differentially expressed between HCC and NH individuals in all three cohorts. Five upregulated miRNAs (miR-122-5p, miR-125b-5p, miR-885-5p, miR-100-5p and miR-148a-3p) in CHB, cirrhosis and HCC patients are potential biomarkers for CHB infection, while miR-34a-5p can be a biomarker for cirrhosis. Notably, four miRNAs (miR-1972, miR-193a-5p, miR-214-3p and miR-365a-3p) can distinguish HCC from other non-HCC individuals. Six miRNAs are potential prognostic markers for overall survival.