鉴定和验证与铁死亡相关的 lncRNA 特征作为结肠癌的一种新的预后模型。
Identification and Validation of Ferroptosis-Related LncRNA Signatures as a Novel Prognostic Model for Colon Cancer.
机构信息
Department of Gastrointestinal Surgery, The Third XiangYa Hospital of Central South University, Changsha, China.
School of Life Sciences, Central South University, Changsha, China.
出版信息
Front Immunol. 2022 Jan 26;12:783362. doi: 10.3389/fimmu.2021.783362. eCollection 2021.
BACKGROUND
Ferroptosis is a newly defined form of programmed cell death that plays an important role in many cancers. However, ferroptosis-related lncRNAs (FRLs) involved in the regulation of colon cancer are not thoroughly understood. This study aimed to identify a prognostic FRL signature in colon cancer and explore its potential molecular function.
METHODS
RNA-seq data and relevant clinical information were obtained from The Cancer Genome Atlas (TCGA) database, and a list of ferroptosis-related genes was extracted from the FerrDb website. Analysis of differentially expressed FRLs was performed using the 'limma' package in R software. By implementing coexpression analysis and univariate Cox analysis, we then identified prognostic FRLs. Using Cox regression analysis with the least absolute shrinkage and selection operator (LASSO) algorithm, we constructed a prognostic model based on 4 FRLs. We evaluated the prognostic power of this model using Kaplan-Meier (K-M) survival curve analysis and receiver operating characteristic (ROC) curve analysis. Moreover, the relationships between the signature and immune landscape, somatic mutation and drug sensitivity were explored. Finally, experiments were conducted to validate the functions of AP003555.1 and AC000584.1.
RESULTS
A 4-FRL signature was constructed. Two risk groups were classified based on the risk score calculated by this signature. The signature-based risk score exhibited a more powerful capacity for survival prediction than traditional clinicopathological features in colon patients. Additionally, we observed a significant difference in immune cells, such as CD4+ and CD8+ T cells and macrophages, between the two groups. Moreover, the high-risk group exhibited lower IC50 values for certain chemotherapy drugs, such as cisplatin, docetaxel, bleomycin or axitinib. Finally, the experiments showed that ferroptosis processes were suppressed after AP003555.1 and AC000584.1 knockdown.
CONCLUSION
The proposed 4-FRL signature is a promising biomarker to predict clinical outcomes and therapeutic responses in colon cancer patients.
背景
铁死亡是一种新定义的程序性细胞死亡形式，在许多癌症中发挥着重要作用。然而，参与调控结肠癌的铁死亡相关长非编码 RNA（FRLs）尚未被充分了解。本研究旨在鉴定结肠癌中一个与预后相关的 FRL 特征，并探索其潜在的分子功能。
方法
从癌症基因组图谱（TCGA）数据库中获取 RNA-seq 数据和相关临床信息，并从 FerrDb 网站提取铁死亡相关基因列表。使用 R 软件中的 'limma' 包进行差异表达 FRL 分析。通过共表达分析和单变量 Cox 分析，我们确定了与预后相关的 FRLs。使用 Cox 回归分析和最小绝对收缩和选择算子（LASSO）算法，我们基于 4 个 FRL 构建了一个预后模型。我们使用 Kaplan-Meier（K-M）生存曲线分析和接收器操作特征（ROC）曲线分析评估该模型的预后能力。此外，还探索了该特征与免疫景观、体细胞突变和药物敏感性之间的关系。最后，进行了实验以验证 AP003555.1 和 AC000584.1 的功能。
结果
构建了一个 4-FRL 特征。根据该特征计算的风险评分将结肠癌患者分为两个风险组。该特征的风险评分在预测结肠癌患者的生存方面比传统的临床病理特征更具优势。此外，我们观察到两组之间免疫细胞（如 CD4+和 CD8+T 细胞和巨噬细胞）存在显著差异。此外，高风险组对某些化疗药物（如顺铂、多西他赛、博来霉素或阿昔替尼）的 IC50 值较低。最后，实验表明，AP003555.1 和 AC000584.1 敲低后，铁死亡过程受到抑制。
结论
提出的 4-FRL 特征是预测结肠癌患者临床结局和治疗反应的有前途的生物标志物。
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