Center of Excellence in Hepatitis and Liver Cancer, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
PLoS One. 2020 Apr 24;15(4):e0232211. doi: 10.1371/journal.pone.0232211. eCollection 2020.
Circulating microRNAs (miRNAs) have been shown to dysregulate in many cancer types including hepatocellular carcinoma (HCC). The purpose of this study was to examine the potential diagnostic or prognostic roles of circulating miRNAs in patients with hepatitis B virus (HBV)-related HCC.
Paired cancerous and adjacent non-cancerous liver tissue specimens of patients with HBV-related HCC were used as a discovery set for screening 800 miRNAs by a Nanostring quantitative assay. Differentially expressed miRNAs were then examined by SYBR green quantitative RT-PCR in a validation cohort of serum samples obtained from 70 patients with HBV-related HCC, 70 HBV patients without HCC and 50 healthy controls.
The discovery set identified miR-223-3p, miR-199a-5p and miR-451a significantly lower expressed in cancerous tissues compared with non-cancerous tissues. In the validated cohort, circulating miR-223-3p levels were significantly lower in the HCC group compared with the other groups. The combined use of serum alpha-fetoprotein and miR-223-3p displayed high sensitivity for detecting early HCC (85%) and intermediate/advanced stage HCC (100%). Additionally, serum miR-223-3p had a negative correlation with tumor size and BCLC stage. On multivariate analysis, serum miR-223-3p was identified as an independent prognostic factor of overall survival in patients with HCC. In contrast, circulating miRNA-199a-5p and miR-451a did not show any clinical benefit for the diagnosis and prognostic prediction of HCC.
Our results demonstrated that miR-223-3p was differentially expressed in cancerous compared with paired adjacent non-cancerous tissues. In addition, circulating miRNA-223-3p could represent a novel diagnostic and prognostic marker for patients with HBV-related HCC.
循环 microRNAs（miRNAs）在包括肝细胞癌（HCC）在内的许多癌症类型中被证明失调。本研究的目的是研究循环 miRNAs 在乙型肝炎病毒（HBV）相关 HCC 患者中的潜在诊断或预后作用。
使用配对的 HBV 相关 HCC 癌组织和相邻非癌组织标本作为发现集，通过 Nanostring 定量测定筛选 800 个 miRNAs。然后，在 70 例 HBV 相关 HCC 患者、70 例 HBV 无 HCC 患者和 50 例健康对照者的血清样本验证队列中，通过 SYBR 绿色定量 RT-PCR 检查差异表达的 miRNAs。
发现集确定 miR-223-3p、miR-199a-5p 和 miR-451a 在癌组织中的表达明显低于非癌组织。在验证队列中，与其他组相比，HCC 组血清 miR-223-3p 水平明显较低。血清α-胎蛋白和 miR-223-3p 的联合使用对检测早期 HCC（85%）和中/晚期 HCC（100%）具有较高的敏感性。此外，血清 miR-223-3p 与肿瘤大小和 BCLC 分期呈负相关。多因素分析显示，血清 miR-223-3p 是 HCC 患者总生存的独立预后因素。相比之下，循环 miRNA-199a-5p 和 miR-451a 对 HCC 的诊断和预后预测没有任何临床益处。
我们的结果表明，miR-223-3p 在癌组织中与配对的相邻非癌组织相比表达差异。此外，循环 miRNA-223-3p 可能是 HBV 相关 HCC 患者的一种新的诊断和预后标志物。
