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血清外泌体长非编码 RNA 作为肝细胞癌诊断和预后的标志物。

Serum Exosomal Long Noncoding RNAs and for the Diagnosis and Prognosis of Hepatocellular Carcinoma.

机构信息

Department of Laboratory Medicine, Hangzhou First People's Hospital, Hangzhou, China.

出版信息

Cancer Epidemiol Biomarkers Prev. 2018 Jun;27(6):710-716. doi: 10.1158/1055-9965.EPI-17-0770. Epub 2018 Apr 12.

Abstract

Increasing studies suggest that long noncoding RNAs (lncRNAs) are involved in carcinogenesis of human cancers and might be used as diagnostic biomarkers for cancers. A total of 301 participants were recruited in the first part of the study, including a hepatocellular carcinoma (HCC) group ( = 60), liver cirrhosis (LC) group ( = 85), chronic hepatitis B (CHB) group ( = 96), and healthy subjects ( = 60). In the second part, we collected 55 HCC patients, 60 CHB patients, and 60 healthy subjects as an independent cohort to validate the ability of the experiential lncRNAs for identifying HCC from CHB. A commercial kit was used to isolate serum exosomes and total RNA. The relative levels of lnRNAs and mRNA were measured with TaqMan PCR. The results showed that the levels of and in the HCC group were significantly higher than those in the other groups (all < 0.05). A high level in HCC was associated with portal vein tumor emboli, lymph node metastasis, TNM stage, and overall survival (OS; all < 0.05), and a high level was related to lymph node metastasis, TNM stage, and OS (all < 0.05). discriminated HCC from CHB, gaining an area under the ROC curve (AUC) of 0.719 (cutoff value of 1.345); gained an AUC of 0.750 (cutoff value of 1.690). Furthermore, the AUC for the combination of the 2 lncRNAs and serum AFP (cutoff value of 20 μg/L) was 0.894. The abilities of the 2 lncRNAs for identifying HCC from CHB were validated by an independent cohort. The results suggested that the combination of serum exosomal , , and AFP may be a valuable assay in diagnosis and prognosis of HCC. Our data will shed light on exosomal lncRNAs as biomarkers for HCC. .

摘要

越来越多的研究表明,长链非编码 RNA(lncRNA)参与人类癌症的发生,并且可以作为癌症的诊断生物标志物。在研究的第一部分,共招募了 301 名参与者,包括肝细胞癌(HCC)组(=60)、肝硬化(LC)组(=85)、慢性乙型肝炎(CHB)组(=96)和健康对照组(=60)。在第二部分,我们收集了 55 例 HCC 患者、60 例 CHB 患者和 60 例健康对照者作为独立队列,以验证经验性 lncRNA 识别 HCC 与 CHB 的能力。使用商业试剂盒分离血清外泌体和总 RNA。采用 TaqMan PCR 测定 lncRNA 和 mRNA 的相对水平。结果表明,HCC 组和其他各组相比,lncRNA 和 mRNA 的水平均显著升高(均 P < 0.05)。HCC 中高水平与门静脉癌栓、淋巴结转移、TNM 分期和总生存(OS;均 P < 0.05)相关,高水平与淋巴结转移、TNM 分期和 OS 相关(均 P < 0.05)。lncRNA 区分 HCC 与 CHB,ROC 曲线下面积(AUC)为 0.719(截断值为 1.345);lncRNA 获得 AUC 为 0.750(截断值为 1.690)。此外,2 个 lncRNA 与血清 AFP(截断值为 20 μg/L)联合的 AUC 为 0.894。2 个 lncRNA 区分 HCC 与 CHB 的能力在独立队列中得到验证。结果表明,血清外泌体 lncRNA 、和 AFP 的联合检测可能是 HCC 诊断和预后的有价值的检测方法。我们的数据将为外泌体 lncRNA 作为 HCC 生物标志物提供新的见解。

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