Division of Cellular & Molecular Research, National Cancer Centre Singapore, Singapore, Singapore.
Department of Hepato-pancreato-biliary & Transplant Surgery, Singapore General Hospital, Singapore, Singapore.
Sci Rep. 2019 Jul 18;9(1):10464. doi: 10.1038/s41598-019-46872-8.
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 3 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.
肝细胞癌（HCC）是第五种最常见的癌症，死亡率很高，这是由于诊断较晚和治疗选择有限。循环血液中的 microRNA 以高度稳定的无细胞形式存在，有望成为 HCC 早期检测的新型潜在生物标志物。我们进行了全 microRNA 组谱分析，以鉴定 HCC 与正常健康（NH）志愿者之间失调的 microRNA。这些失调的 microRNA 在独立的 HCC、NH 和慢性乙型肝炎（CHB）志愿者队列中得到验证，最后在包括 NH、CHB、肝硬化和 HCC 志愿者的 3 个队列中进行验证，以评估疾病进展过程中的 microRNA 变化。分析循环 microRNA 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 个 microRNA 存在差异表达。在 CHB、肝硬化和 HCC 患者中上调的 5 个 microRNA（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 可以作为肝硬化的生物标志物。值得注意的是，有 4 个 microRNA（miR-1972、miR-193a-5p、miR-214-3p 和 miR-365a-3p）可以将 HCC 与其他非 HCC 个体区分开来。有 6 个 microRNA 是总生存期的潜在预后标志物。
