Purpose: Ferroptosis and long non-coding RNA (lncRNA) expression signatures have been associated with the clinical progression and immune-contexture of different solid tumors. The study aimed to identify a prognostic signature of ferroptosis-related lncRNAs (falncRNAs) to forecast the immune scenery and immunotherapy response in esophageal cancer (EC).
Patients and Methods: Gene expression profiles of EC were extracted from The Cancer Genome Atlas (TCGA) database, and ferroptosis-related genes were downloaded from the FerrDb database, which identified differentially expressed falncRNAs (DEfalncRNAs) via differential analysis. DEfalncRNA pairs associated with prognosis were identified by constructing a matrix, univariate and least absolute shrinkage and selection operator (LASSO) analysis. The prognostic signature was constructed by multivariate analysis. We appraised the forecasting capability of prognostic signature in survival, clinicopathological features, immune landscape, efficacy of immunotherapy, and drug sensitivity. The potential molecular mechanism of signature was investigated by gene set enrichment analysis (GSEA).
Results: We obtained 18 DEfalncRNA pairs to define a novel prognostic signature that was determined on a discovery cohort of 158 tumor samples and 11 adjacent normal tissues from TCGA and internally validated, with the definition of high- vs low-risk groups based on 3 years overall survival. We demonstrated that the high- vs low-risk groups differed for clinical parameters and computationally predicted drug sensitivity and tumor immune contexture, with the high-risk group having worse survival, more aggressive disease (node involvement, metastasis), reduced drug sensitivity, higher tumor mutation load, and gene signatures of infiltration of pro-tumoral immune cell subsets. The GSEA results revealed that ferroptosis and immunoregulatory pathways were significantly enriched in the high-risk group.
Conclusion: The prognostic signature based on falncRNAs has the potential to forecast the survival, immune scenery, efficacy of immunotherapy, and drug sensitivity of EC, which is helpful for clinical prediction and individualized treatment.

Keywords: esophageal cancer, ferroptosis, lncRNA, immune, signature, prognosis


中文翻译：

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铁死亡相关 LncRNA 的有希望的食管癌预后特征可预测免疫情况和免疫治疗反应

目的：铁死亡和长链非编码 RNA (lncRNA) 表达特征与不同实体瘤的临床进展和免疫结构相关。该研究旨在确定铁死亡相关 lncRNA (falncRNA) 的预后特征，以预测食管癌 (EC) 的免疫情况和免疫治疗反应。
患者和方法：从癌症基因组图谱（TCGA）数据库中提取EC的基因表达谱，从FerrDb数据库下载铁死亡相关基因，通过差异分析鉴定差异表达的falncRNAs（DEfalncRNAs）。通过构建矩阵、单变量和最小绝对收缩和选择算子 (LASSO) 分析来确定与预后相关的 DEfalncRNA 对。通过多变量分析构建预后特征。我们评估了预后特征在生存、临床病理学特征、免疫景观、免疫治疗效果和药物敏感性方面的预测能力。通过基因集富集分析（GSEA）研究了签名的潜在分子机制。
结果：我们获得了 18 个 DEfalncRNA 对来定义一个新的预后特征，该特征是在来自 TCGA 的 158 个肿瘤样本和 11 个相邻正常组织的发现队列中确定的，并经过内部验证，根据 3 年总生存率定义高风险组和低风险组. 我们证明了高风险组和低风险组在临床参数和计算预测的药物敏感性和肿瘤免疫环境方面存在差异，高风险组的生存率更差，疾病更具侵袭性（淋巴结受累，转移），药物敏感性降低，更高肿瘤突变负荷和促肿瘤免疫细胞亚群浸润的基因特征。GSEA结果显示，铁死亡和免疫调节途径在高危组中显着富集。
结论：基于 falncRNAs 的预后特征具有预测 EC 的存活率、免疫情况、免疫治疗效果和药物敏感性的潜力，有助于临床预测和个体化治疗。

关键词：食管癌，铁死亡，lncRNA，免疫，特征，预后