Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan.
Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Liver Int. 2021 May;41(5):956-968. doi: 10.1111/liv.14772. Epub 2021 Jan 23.
BACKGROUND & AIMS: Differentiation antagonizing non-protein coding RNA is associated with various types of neoplasms. Hepatitis C virus-related hepatocellular carcinoma has a high risk of recurrence. Here we determined the role of differentiation antagonizing non-protein coding RNA in hepatitis C virus-related hepatocarcinogenesis and identified potential therapeutic targets and non-invasive prognostic markers for long-term outcome of hepatitis C virus-related hepatocellular carcinoma after surgical resection.
Differentiation antagonizing non-protein coding RNAs relevant to hepatitis C virus-related hepatocellular carcinoma were identified through comparative RNA-sequencing of tumour and adjacent non-tumour (ANT) tissues in a screening set, and were validated using real-time polymerase chain reaction. Target long non-coding RNAs (lncRNAs) in tissues and serum exosomes were used to predict the recurrence of hepatitis C virus-related hepatocellular carcinoma after curative surgical resection in a large application cohort from 2005 to 2012.
We confirmed that differentiation antagonizing non-protein coding RNA was upregulated following hepatitis C virus infection and identified as the lncRNA most relevant to hepatitis C virus-related hepatocellular carcinoma in tumour tissues as compared to that in ANT tissues. In 183 hepatitis C virus-related hepatocellular carcinoma patients followed for 10 years after curative HCC resection, the expression level of circulating exosomal differentiation antagonizing non-protein coding RNA was positively associated with HCC recurrence and was the most predictive factor associated with HCC recurrence and mortality (hazard ratio/95% confidence intervals: 7.0/4.3-11.6 and 2.7/1.5-5.1 respectively).
Differentiation antagonizing non-protein coding RNA is highly relevant to disease progression of hepatitis C virus-related hepatocellular carcinoma. Our finding indicated that circulating exosomal differentiation antagonizing non-protein coding RNA might serve as a non-invasive prognostic biomarker for hepatitis C virus-related hepatocellular carcinoma.
分化拮抗非编码 RNA 与多种类型的肿瘤有关。丙型肝炎病毒相关肝细胞癌具有较高的复发风险。在这里，我们确定了分化拮抗非编码 RNA 在丙型肝炎病毒相关肝细胞癌发生中的作用，并确定了潜在的治疗靶点和非侵入性预后标志物，用于预测丙型肝炎病毒相关肝细胞癌手术后的长期结果。
通过对筛选集中肿瘤和相邻非肿瘤（ANT）组织的比较 RNA 测序，确定与丙型肝炎病毒相关肝细胞癌相关的分化拮抗非编码 RNA，并通过实时聚合酶链反应进行验证。组织和血清外泌体中的靶长链非编码 RNA（lncRNA）用于预测 2005 年至 2012 年期间一个大型应用队列中丙型肝炎病毒相关肝细胞癌根治性手术后的复发。
我们证实，丙型肝炎病毒感染后分化拮抗非编码 RNA 上调，并确定其为肿瘤组织中与丙型肝炎病毒相关肝细胞癌最相关的 lncRNA，与 ANT 组织相比。在 183 例丙型肝炎病毒相关肝细胞癌患者中，对他们进行了 10 年的根治性 HCC 切除术后随访，循环外泌体分化拮抗非编码 RNA 的表达水平与 HCC 复发呈正相关，是与 HCC 复发和死亡率最相关的预测因素（危险比/95%置信区间：7.0/4.3-11.6 和 2.7/1.5-5.1）。
分化拮抗非编码 RNA 与丙型肝炎病毒相关肝细胞癌的疾病进展高度相关。我们的发现表明，循环外泌体分化拮抗非编码 RNA 可能作为丙型肝炎病毒相关肝细胞癌的一种非侵入性预后生物标志物。
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