Zhou Chenghui, Zhang Huajun, Lu Liqing
Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China.
Department of General, Visceral, Cancer and Transplantation Surgery, University Hospital Cologne, Cologne, Germany.
Front Genet. 2021 Sep 28;12:744113. doi: 10.3389/fgene.2021.744113. eCollection 2021.
Hepatocellular carcinoma (HCC) is one of the most general malignant tumors. Hypoxia is a critical clinical characteristic and acts as a significant part in the development and cancers' prognosis. The prognostic value and biological functions of hypoxia-related lncRNAs in hepatocellular carcinoma is little known. Thus, we aim to establish a hypoxia-related lncRNA signature to predict the HCC patients' survival. First, we extracted the hypoxia-related genes and expression of lncRNAs from the MSigDB and TCGA database, respectively. The co-expression analysis among hypoxia-related mRNAs and lncRNAs was employed to identify hypoxia-related lncRNAs. Then, comprehensive analyses of lncRNAs expression level and survival data were applied to establish the signature. We built a prognostic signature on the foundation of the three differently expressed hypoxia-related lncRNAs. Kaplan-Meier curves indicated the low-risk group is associated with better survival. The 1-, 3-, and 5 years AUC values of the signature were 0.805, 0.672 and 0.63 respectively. The test set performed consistent outcomes. A nomogram was built grounded on the risk score and clinicopathological features. GSEA showed the immune-related pathways in high-risk group, while metabolism-related pathways in low-risk group. Besides, we found this model was correlated with the clinical features, tumor immune cell infiltration, immune checkpoints, and m6A-related genes. Finally, a novel signature based on hypoxia-related lncRNAs was established and validated for predicting HCC patients' survival and may offer some useful information for immunotherapies.
肝细胞癌（HCC）是最常见的恶性肿瘤之一。缺氧是一个关键的临床特征，在肿瘤的发生发展及预后中起着重要作用。缺氧相关lncRNA在肝细胞癌中的预后价值和生物学功能鲜为人知。因此，我们旨在建立一种基于缺氧相关lncRNA的特征来预测HCC患者的生存情况。首先，我们分别从MSigDB和TCGA数据库中提取缺氧相关基因和lncRNA的表达数据。通过对缺氧相关mRNA和lncRNA进行共表达分析来鉴定缺氧相关lncRNA。然后，综合分析lncRNA表达水平和生存数据以建立特征。我们基于三种差异表达的缺氧相关lncRNA构建了一个预后特征。Kaplan-Meier曲线表明低风险组的生存情况更好。该特征的1年、3年和5年AUC值分别为0.805、0.672和0.63。验证集得到了一致的结果。基于风险评分和临床病理特征构建了列线图。基因集富集分析（GSEA）显示高风险组中与免疫相关的通路，而低风险组中与代谢相关的通路。此外，我们发现该模型与临床特征、肿瘤免疫细胞浸润、免疫检查点和m6A相关基因有关。最后，建立并验证了一种基于缺氧相关lncRNA的新型特征，用于预测HCC患者的生存情况，可为免疫治疗提供一些有用信息。
