一个与肝细胞癌预后、肿瘤免疫微环境和基因组不稳定性相关的铁死亡相关长非编码 RNA 特征。
A Ferroptosis-Related LncRNA Signature Associated with Prognosis, Tumor Immune Environment, and Genome Instability in Hepatocellular Carcinoma.
机构信息
Department of Outpatient Chemotherapy, Harbin Medical University Cancer Hospital, Harbin, 150000 Heilongjiang Province, China.
Department of Gynecology and Obstetrics, Medical Faculty, Justus-Liebig-University Giessen, 35390, Giessen, Germany.
出版信息
Comput Math Methods Med. 2022 Aug 18;2022:6284540. doi: 10.1155/2022/6284540. eCollection 2022.
BACKGROUND
Ferroptosis is an iron-dependent form of cell death. In this study, we identified ferroptosis-related long noncoding RNAs (FRlncRNAs) to investigate their association with hepatocellular carcinoma (HCC) in prognosis, tumor immune environment, and genome instability.
METHODS
Transcriptome profile data of HCC were retrieved from a public database. FRlncRNAs were identified by co-expression analysis. Patients were randomly divided into training and test cohorts. Univariate Cox analysis and Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression were performed to construct a risk model. Patients were divided into high- and low-risk groups based on the risk model. AUC and C index were used to assess the risk model. Survival analysis, immune status, and genome instability were compared between the two groups.
RESULTS
Sixteen FRlncRNAs were identified and used to construct an FRlncRNA signature for the risk model. The Kaplan-Meier analysis revealed that patients in the high-risk group had poorer overall survival than patients in the low-risk group. The area under curve of the risk model was 0.879, 0.809, and 0.757 in the training cohort and 0.635, 0.688, and 0.739 in the test cohort at 1, 2, and 3 years, respectively. The risk model was an independent prognostic predictor and showed excellent prediction of prognosis compared with clinicopathological features. For the differentially expressed ferroptosis-related genes, many enriched metabolic pathways were identified in the functional enrichment analysis. Immune cells such as CD8+ T cells, macrophages M1, natural killer cells, and B cells, which may be associated with antitumor immune responses, differed between the high- and low-risk groups. Genome instability based on the risk model was also explored. A total of 61 genes were differently mutated between the two risk groups, and among them, , , , , and had the most significant mutation frequency differences.
CONCLUSION
The FRlncRNA signature is closely related with overall survival, tumor immune environment, and genome instability in HCC.
背景
铁死亡是一种依赖铁的细胞死亡形式。本研究通过共表达分析鉴定了与肝细胞癌（HCC）相关的铁死亡相关长非编码 RNA（FRlncRNAs），以研究其与 HCC 预后、肿瘤免疫环境和基因组不稳定性的关系。
方法
从公共数据库中检索 HCC 的转录组谱数据。通过共表达分析鉴定 FRlncRNAs。将患者随机分为训练集和测试集。采用单因素 Cox 分析和最小绝对值收缩和选择算子（LASSO）Cox 回归构建风险模型。根据风险模型将患者分为高风险组和低风险组。采用 AUC 和 C 指数评估风险模型。比较两组之间的生存分析、免疫状态和基因组不稳定性。
结果
鉴定出 16 个 FRlncRNAs，并用于构建风险模型的 FRlncRNA 特征。Kaplan-Meier 分析显示，高风险组患者的总生存率低于低风险组患者。风险模型在训练集的 AUC 分别为 0.879、0.809 和 0.757，在测试集的 AUC 分别为 0.635、0.688 和 0.739，在 1、2 和 3 年时分别为 0.635、0.688 和 0.739。风险模型是独立的预后预测因子，与临床病理特征相比，具有优异的预后预测能力。对于差异表达的铁死亡相关基因，在功能富集分析中鉴定出许多富集的代谢途径。高风险组和低风险组之间的免疫细胞存在差异，如 CD8+T 细胞、M1 巨噬细胞、自然杀伤细胞和 B 细胞，这些细胞可能与抗肿瘤免疫反应有关。还探索了基于风险模型的基因组不稳定性。在两组风险之间，共有 61 个基因发生了不同的突变，其中 、 、 、 、 和 具有最显著的突变频率差异。
结论
FRlncRNA 特征与 HCC 的总生存率、肿瘤免疫环境和基因组不稳定性密切相关。
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