新型长非编码 RNA 标志物对乙型肝炎病毒相关肝细胞癌患者肝切除术后的预后影响及其与临床分期系统的比较。
Prognostic effect of a novel long noncoding RNA signature and comparison with clinical staging systems for patients with hepatitis B virus-related hepatocellular carcinoma after hepatectomy.
机构信息
Department of Gastroenterology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, China.
Shandong Provincial Engineering and Technological Research Center for Liver Diseases Prevention and Control, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, China.
出版信息
J Dig Dis. 2020 Nov;21(11):650-663. doi: 10.1111/1751-2980.12941. Epub 2020 Oct 27.
OBJECTIVES
We aimed to establish a novel prognostic long noncoding RNA (lncRNA) signature for hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) patients after hepatectomy and to validate its prognostic efficacy compared with other clinical staging systems.
METHODS
Expression data of 374 HCC samples were retrieved from The Cancer Genome Atlas (TCGA) database. Cox regression analyses were performed to develop the lncRNA model. The expression levels of lncRNAs were detected by qualitative real-time polymerase chain reaction (qRT-PCR) in HBV-HCC. Then the qRT-PCR-based signature and nomogram were constructed and compared with those of other clinical staging systems in a clinical cohort and qRT-PCR, RNA fluorescent in situ hybridization and comprehensive bioinformatics analyses were conducted.
RESULTS
The signature containing five lncRNAs was constructed through TCGA. This model showed the highest predictive efficacy in patients with HBV-HCC. Compared with normal liver tissues, all lncRNAs were highly expressed in HBV-HCC. A four-lncRNA signature containing LINC01116, DDX11-AS1, LUCAT1 and FIRRE was developed based on the qRT-PCR data in a clinical HBV-HCC patient cohort. A Kaplan-Meier analysis indicated that the low-risk group had significantly longer overall survival than the high-risk group. Additionally, the qRT-PCR-based four-lncRNA formula was an independent prognostic factor and had better predictive efficacy for survival (area under the receiver operating characteristic curve 0.875) compared with other clinical staging systems in HBV-HCC. The lncRNA-mRNA co-expression and enrichment analyses revealed the potential regulatory mechanisms of the lncRNA identified.
CONCLUSION
The four-lncRNA model may be an effective prognostic signature and provides potential prognostic biomarkers and therapeutic targets for HBV-HCC.
目的
我们旨在建立一种新的与乙型肝炎病毒相关的肝癌（HBV-HCC）患者肝切除术后的预后长链非编码 RNA（lncRNA）标志物，并验证其与其他临床分期系统相比的预后疗效。
方法
从癌症基因组图谱（TCGA）数据库中检索了 374 例 HCC 样本的表达数据。通过 Cox 回归分析建立 lncRNA 模型。通过实时荧光定量聚合酶链反应（qRT-PCR）检测 HBV-HCC 中 lncRNA 的表达水平。然后构建基于 qRT-PCR 的签名和列线图，并与其他临床分期系统在临床队列和 qRT-PCR、RNA 荧光原位杂交和综合生物信息学分析中进行比较。
结果
该模型通过 TCGA 构建，包含五个 lncRNA。该模型在 HBV-HCC 患者中显示出最高的预测疗效。与正常肝组织相比，所有 lncRNA 在 HBV-HCC 中均高度表达。基于临床 HBV-HCC 患者队列中的 qRT-PCR 数据，开发了包含 LINC01116、DDX11-AS1、LUCAT1 和 FIRRE 的四个 lncRNA 标志物。Kaplan-Meier 分析表明，低风险组的总生存期明显长于高风险组。此外，基于 qRT-PCR 的四-lncRNA 公式是独立的预后因素，与 HBV-HCC 中的其他临床分期系统相比，具有更好的生存预测疗效（接受者操作特征曲线下面积 0.875）。lncRNA-mRNA 共表达和富集分析揭示了所鉴定的 lncRNA 的潜在调控机制。
结论
该四-lncRNA 模型可能是一种有效的预后标志物，为 HBV-HCC 提供了潜在的预后生物标志物和治疗靶点。
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