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联合检测血清中三个 lncRNAs 作为乙型肝炎病毒相关肝细胞癌的有效诊断和预后生物标志物。

Combined identification of three lncRNAs in serum as effective diagnostic and prognostic biomarkers for hepatitis B virus-related hepatocellular carcinoma.

机构信息

Department of Clinical Laboratory, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.

Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.

出版信息

Int J Cancer. 2022 Nov 15;151(10):1824-1834. doi: 10.1002/ijc.34201. Epub 2022 Jul 25.

Abstract

Hepatitis B virus-related hepatocellular carcinoma (HBV-related HCC) is a common, highly invasive malignant tumor associated with a high mortality rate. This study aimed to identify the effective diagnostic and prognostic biomarkers for HBV-related HCC. With HBV-related HCC RNA-sequencing data of The Cancer Genome Atlas (TCGA) database, 159 differentially expressed long noncoding RNAs (lncRNAs) between HBV-related HCC and para-carcinoma normal samples were identified, and 12 lncRNAs were eventually assessed for deeper research. Classification analysis developed a three-lncRNA signature of AC005332.5, ELF3-AS1 and LINC00665, which was demonstrated to be the most discriminatory with an AUC (Area under the curve) value of 0.913 (95% CI: 0.8610-0.9665) and verified in validation patients. The expression levels of AC005332.5, ELF3-AS1 and LINC00665 were significantly changed with different tumor stages or grades. Survival analysis revealed that AC005332.5, ELF3-AS1 and LINC00665 were highly associated with the prognosis of overall survival. Additionally, the lncRNA signature yielded statistical significance to predict clinical outcomes independently from other clinical variables in validation patients, as suggested in the multivariate Cox hazards analysis. Conclusively, a three-lncRNA signature of AC005332.5, ELF3-AS1 and LINC00665 may serve as an excellent diagnostic biomarker for HBV-related HCC and potential prognostic significance for HBV-related HCC sufferers.

摘要

乙型肝炎病毒相关性肝细胞癌(HBV-related HCC)是一种常见的、高度侵袭性的恶性肿瘤,死亡率较高。本研究旨在寻找 HBV 相关 HCC 的有效诊断和预后生物标志物。利用 TCGA 数据库中 HBV 相关 HCC 的 RNA 测序数据,鉴定出 HBV 相关 HCC 与癌旁正常样本之间存在 159 个差异表达的长非编码 RNA(lncRNA),最终评估了 12 个 lncRNA 进行更深入的研究。分类分析开发了一个由 AC005332.5、ELF3-AS1 和 LINC00665 组成的三 lncRNA 特征,该特征具有最高的区分能力,AUC(曲线下面积)值为 0.913(95%CI:0.8610-0.9665),并在验证患者中得到验证。AC005332.5、ELF3-AS1 和 LINC00665 的表达水平随着肿瘤不同的分期或分级而显著改变。生存分析显示,AC005332.5、ELF3-AS1 和 LINC00665 与总生存期的预后高度相关。此外,该 lncRNA 特征在验证患者中独立于其他临床变量,在多变量 Cox 危害分析中提示具有统计学意义,可以预测临床结局。综上所述,AC005332.5、ELF3-AS1 和 LINC00665 的三 lncRNA 特征可作为 HBV 相关 HCC 的一种优秀诊断生物标志物,具有潜在的预后意义。

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