Rao Yamin, Zhu Jinchao, Zheng Haiyan, Dong Wei, Lin Qingyuan
Department of Pathology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Pathology, Eastern Hepatobilliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
Front Oncol. 2022 Oct 12;12:929960. doi: 10.3389/fonc.2022.929960. eCollection 2022.
Ferroptosis is an iron-dependent programmed cell death related to the biological process of many kinds of tumors. Long noncoding RNAs ( have been found to play essential roles in the tumor, and their functions in the ferroptosis of tumor cells have been partially discovered. However, there is no summary of ferroptosis-related and its functions in melanoma. In the present study, we aim to explore the expression profile of ferroptosis-related genes and their value in melanoma prognosis by bioinformatics analysis. The expression of ferroptosis-related gene () from melanoma clinical data was extracted based on the Cancer Genome Atlas () database. By screening the expression data of 472 cases of melanoma and 810 cases of normal skin, eighteen ferroptosis-related differential genes were found to be related to the overall survival rate. Furthermore, 384 ferroptosis-related were discovered through constructing the co-expression network, and ten of them were found with prognostic significance in melanoma by multivariate Cox analysis. Risk assessment showed that the high expression of is associated with poor prognosis, while the increased expression of the other LncRNA is beneficial to the prognosis of patients with melanoma. From univariate and multivariate Cox regression analysis, there were ten ferroptosis-related LncRNA risk models towards to be significant independent prognostic factors for patients with melanoma and valuable predictive factors for overall survival ()(P<0.05). The curve further suggested that the risk score has relatively reliable predictive ability (=0.718). The protein level of ferroptosis-related genes was verified by the database and test, leading to the discovery that the expressions of , , , and proteins up-regulated in tumor tissues, and existed differences between tumor tissues and normal tissues. In conclusion, we identified ten ferroptosis-related and constructed a prognosis model base.
铁死亡是一种与多种肿瘤生物学过程相关的铁依赖性程序性细胞死亡。长链非编码RNA（lncRNAs）已被发现在肿瘤中发挥重要作用，并且它们在肿瘤细胞铁死亡中的功能已被部分发现。然而，目前尚无关于黑色素瘤中铁死亡相关lncRNAs及其功能的总结。在本研究中，我们旨在通过生物信息学分析探索铁死亡相关基因的表达谱及其在黑色素瘤预后中的价值。基于癌症基因组图谱（TCGA）数据库提取黑色素瘤临床数据中铁死亡相关基因（lncRNAs）的表达。通过筛选472例黑色素瘤和810例正常皮肤的lncRNAs表达数据，发现18个铁死亡相关差异基因与总生存率相关。此外，通过构建lncRNA共表达网络发现了384个铁死亡相关lncRNAs，其中10个通过多变量Cox分析在黑色素瘤中具有预后意义。风险评估显示，某lncRNA的高表达与预后不良相关，而其他lncRNA的表达增加有利于黑色素瘤患者的预后。单变量和多变量Cox回归分析显示，有10个铁死亡相关lncRNA风险模型对黑色素瘤患者是显著的独立预后因素和总生存（OS）的有价值预测因素（P<0.05）。生存曲线进一步表明风险评分具有相对可靠的预测能力（AUC=0.718）。通过蛋白质图谱数据库和免疫组化检测验证了铁死亡相关基因的蛋白水平，发现某几个蛋白在肿瘤组织中的表达上调，且肿瘤组织与正常组织之间存在差异。总之，我们鉴定了10个铁死亡相关lncRNAs并构建了一个预后模型库。
