Abstract

Hepatocellular carcinoma (HCC) represents the sixth most common cancer worldwide. Cirrhosis induced by hepatitis-C virus (HCV) infection is a key risk factor for HCC. ZNFX1 antisense RNA 1 (ZFAS1), a novel long non-coding RNA (lncRNA) was found to be increased in multiple cancers contributing to cancer development and progression. We aimed to evaluate the expression profile of plasma ZFAS1 in HCV-related HCC and explore its relation to HCC stage. Plasma from 20 HCV-related liver cirrhosis patients without HCC, 60 HCV-related HCC patients with underlying cirrhosis and 20 healthy controls was collected. Subsequently, relative quantification of ZFAS1 lncRNA expression was performed using quantitative real time-polymerase chain reaction. Expression level was significantly higher in HCC compared to cirrhotic patients (p = 0.017). Meanwhile, the area under the receiver operating characteristic curve (AUC) of ZFAS1 expression was 0.700 (95% confidence interval: 0.564–0.836) to differentiate HCC from cirrhotic patients, while that of serum alpha fetoprotein (AFP) was 1.000 (95% confidence interval: 1.000–1.000). Interestingly, there was a positive correlation between ZFAS1 relative expression and Child Pugh classification in HCC group (p = 0.039). In conclusion, our results indicated that ZFAS1 could be a good diagnostic marker to distinguish HCC from cirrhotic patients with adequate sensitivity and specificity.

中文翻译：

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血浆长链非编码 RNA ZFAS1 作为 HCV 相关肝细胞癌的潜在诊断生物标志物

摘要

肝细胞癌 (HCC) 是全球第六大常见癌症。丙型肝炎病毒 (HCV) 感染引起的肝硬化是 HCC 的关键危险因素。ZNFX1 反义 RNA 1 ( ZFAS1 ) 是一种新型长链非编码 RNA (lncRNA)，被发现在多种癌症中增加，从而导致癌症的发展和进展。我们旨在评估血浆ZFAS1在 HCV 相关 HCC 中的表达谱，并探讨其与 HCC 分期的关系。收集了 20 名未患 HCC 的 HCV 相关肝硬化患者、60 名有潜在肝硬化的 HCV 相关 HCC 患者和 20 名健康对照者的血浆。随后， ZFAS1的相对定量使用定量实时聚合酶链反应进行 lncRNA 表达。与肝硬化患者相比，HCC 中的表达水平显着更高 ( p = 0.017)。同时， ZFAS1表达的接受者操作特征曲线 (AUC) 下面积为 0.700（95% 置信区间：0.564-0.836）以区分 HCC 与肝硬化患者，而血清甲胎蛋白（AFP）为 1.000（95% 置信区间）区间：1.000–1.000）。有趣的是，在 HCC 组中ZFAS1相对表达与 Child Pugh 分级呈正相关（p = 0.039）。总之，我们的结果表明ZFAS1可能是区分 HCC 和肝硬化患者的良好诊断标志物，具有足够的敏感性和特异性。