Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, National Quality Control Center for Donated Organ Procurement, Hubei Key Laboratory of Medical Technology on Transplantation, Hubei Clinical Research Center for Natural Polymer Biological Liver, Hubei Engineering Center of Natural Polymer-based Medical Materials, Wuhan, 430071, Hubei, China.
The 3rd Xiangya Hospital of Central South University, Research Center of National Health Ministry on Transplantation Medicine Engineering and Technology, Changsha, 410013, Hunan, China.
Hum Cell. 2021 Nov;34(6):1830-1842. doi: 10.1007/s13577-021-00607-y. Epub 2021 Sep 6.
Some lncRNA-associated competing endogenous RNAs (ceRNAs) are considered as potential biomarkers for targeted therapies and prognosis in human cancer. In our present study, we aimed to construct a ceRNA network and establish a genomic-clinicopathologic nomogram to provide insights into the molecular mechanisms and predict survival for HBV-related HCC. The Cancer Genome Atlas (TCGA) database was applied to collect the data of LIHC RNA-seq dataset and miRNA-seq dataset as well as the clinicopathological information. Identification of differentially expressed RNAs (mRNAs, lncRNAs, and miRNAs) between HBV-related HCC samples and normal samples was conducted using Limma package in R. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used for performing the functional enrichment analysis of differentially expressed mRNAs. The ceRNA network was carried out using Cytoscape. The LASSO-penalized Cox regression analysis was implemented to identify HCC-related lncRNAs, and the multivariate Cox regression analysis was conducted for the establishment of a genomic-clinicopathology nomogram. A total of 1859 DEmRNAs, 113 DElncRNAs, and 89 DEmiRNAs were screened out etween HBV-related HCC samples and normal samples. A ceRNA network including 44 DEmRNAs, 7 DElncRNAs, and 20 DEmiRNAs was constructed. 7 DElncRNAs (PVT1, LINC01138, LINC02499, AL355488.2, FGF14-AS2, MAFG-AS1 and LINC00261) were finally identified as prognostic indicators. The area under the curve reached 0.8169 for the 7-lncRNA signature. The predictive accuracy and clinical application value were remarkably high for the genomic-clinicopathologic nomogram integrating the histological grade and the 7-gene-based prognostic index. Taken together, we have established a ceRNA network with HBV-related HCC-specific DElncRNAs, DEmiRNAs, and DEmRNAs. Furthermore, the genome-wide data of lncRNA expression were analyzed using the TCGA database, and a 7-lncRNA signature was identified as a potential prognostic predictor for HBV-related HCC patients. Novel functional studies were provided by our current findings for elucidating the molecular mechanism of lncRNA in HBV-related HCC.
一些长链非编码 RNA（lncRNA）相关的竞争性内源 RNA（ceRNA）被认为是人类癌症靶向治疗和预后的潜在生物标志物。在本研究中，我们旨在构建 ceRNA 网络，并建立基因组-临床病理列线图，以深入了解分子机制并预测 HBV 相关 HCC 的生存情况。我们应用癌症基因组图谱（TCGA）数据库收集 LIHC RNA-seq 数据集和 miRNA-seq 数据集以及临床病理信息。使用 R 中的 Limma 软件包鉴定 HBV 相关 HCC 样本与正常样本之间差异表达的 RNA（mRNA、lncRNA 和 miRNA）。使用数据库 for Annotation, Visualization, and Integrated Discovery（DAVID）进行差异表达 mRNAs 的功能富集分析。使用 Cytoscape 进行 ceRNA 网络构建。使用 LASSO 惩罚 Cox 回归分析鉴定 HCC 相关 lncRNA，并进行多变量 Cox 回归分析建立基因组-临床病理列线图。在 HBV 相关 HCC 样本与正常样本之间筛选出 1859 个差异表达的 mRNAs、113 个差异表达的 lncRNAs 和 89 个差异表达的 miRNAs。构建了包含 44 个差异表达的 mRNAs、7 个差异表达的 lncRNAs 和 20 个差异表达的 miRNAs 的 ceRNA 网络。最终确定了 7 个差异表达的 lncRNA（PVT1、LINC01138、LINC02499、AL355488.2、FGF14-AS2、MAFG-AS1 和 LINC00261）作为预后指标。7-lncRNA 特征的曲线下面积达到 0.8169。整合组织学分级和基于 7 个基因的预后指数的基因组-临床病理列线图具有很高的预测准确性和临床应用价值。总之，我们建立了一个包含 HBV 相关 HCC 特异性差异表达的 lncRNA、miRNA 和 mRNA 的 ceRNA 网络。此外，我们使用 TCGA 数据库对 lncRNA 表达的全基因组数据进行了分析，确定了 7-lncRNA 特征作为 HBV 相关 HCC 患者潜在的预后预测因子。我们的研究结果为阐明 lncRNA 在 HBV 相关 HCC 中的分子机制提供了新的功能研究。
