Ferroptosis is a form of iron-dependent programmed cell death. Regulation of ferroptosis in tumor cells is a novel treatment modality. The present study aimed to investigate ferroptosis-related long non-coding RNAs (lncRNAs) and construct a prognostic model for colon adenocarcinoma (COAD). RNA- sequencing data and ferroptosis-related genes were obtained from The Cancer Genome Atlas database and FerrDb database. COAD patients were randomly assigned to training- and validation groups. The Least Absolute Shrinkage and Selection Operator regression and Cox regression model were used to determine and develop a predictive model. The model was corroborated using the validation group and the entire group. In total, 259 ferroptosis-related genes and 905 ferroptosis-related LncRNAs were obtained. Cox model revealed and constructed seven ferroptosis-related LncRNAs signature (LINC01503, AC004687.1, AC010973.2, AP001189.3, ARRDC1-AS1, OIP5-AS1, and NCK1-DT). Patients were assigned into two groups according to the median risk score. Kaplan-Meier survival curves showed that overall survival between high- and low-risk groups was statistically significant (P<0.01). Cox multivariate analysis seven ferroptosis-related LncRNAs signature was an independent risk factor for COAD outcomes (P<0.05). The relationship between seven ferroptosis-related LncRNAs and clinicopathological features was also examined. The principal component analysis showed a difference between high- and low-risk groups intuitively. With the aid of gene set enrichment analysis, the underlying mechanisms of seven ferroptosis-related LncRNAs were uncovered, including the MAPK signaling pathway, mTOR signaling pathway, and glutathione metabolism pathway. Finally, we established and validated seven ferroptosis-related lncRNAs signature for COAD patients to predict survival. These results may provide meaningful targets for future study.

中文翻译：

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结肠癌铁死亡相关 lncRNA 预后特征的开发和验证。

铁死亡是铁依赖性程序性细胞死亡的一种形式。调节肿瘤细胞的铁死亡是一种新的治疗方式。本研究旨在研究铁死亡相关的长非编码RNA（lncRNA）并构建结肠腺癌（COAD）的预后模型。RNA测序数据和铁死亡相关基因从癌症基因组图谱数据库和FerrDb数据库获得。COAD 患者被随机分配到训练组和验证组。使用最小绝对收缩和选择算子回归和 Cox 回归模型来确定和开发预测模型。使用验证组和整个组验证了该模型。总共获得了259个铁死亡相关基因和905个铁死亡相关LncRNA。Cox模型揭示并构建了七个与铁死亡相关的LncRNA特征（LINC01503、AC004687.1、AC010973.2、AP001189.3、ARRDC1-AS1、OIP5-AS1和NCK1-DT）。根据中位风险评分将患者分为两组。Kaplan-Meier生存曲线显示，高危组和低危组的总生存期差异有统计学意义（P<0.01）。Cox多变量分析显示7个与铁死亡相关的LncRNAs特征是COAD结果的独立危险因素（P<0.05）。还检查了七种与铁死亡相关的 LncRNA 与临床病理特征之间的关系。主成分分析直观地显示了高风险组和低风险组之间的差异。借助基因集富集分析，揭示了7种与铁死亡相关的LncRNA的潜在机制，包括MAPK信号通路、mTOR信号通路和谷胱甘肽代谢通路。最后，我们为 COAD 患者建立并验证了七个与铁死亡相关的 lncRNA 特征，以预测生存。这些结果可能为未来的研究提供有意义的目标。