Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Aging (Albany NY). 2022 Aug 14;14(15):6358-6376. doi: 10.18632/aging.204227.
Gastric cancer (GC) is one of the most aggressive malignant tumors worldwide. Ferroptosis is a kind of iron-dependent cell death, which is proved to be closely related to tumor progression. In this study, we aim at constructing a ferroptosis-related lncRNAs signature to predict the prognosis of GC and explore potential therapies.
Ferroptosis-Related LncRNAs Signature for GC patients (FRLSG) was constructed through univariate Cox regression, the LASSO algorithm, and multivariate Cox regression. Kaplan-Meier analysis, receiver operating characteristic curves, and risk score plot were applied to verify the predictive power of FRLSG. Gene Set Enrichment Analysis (GSEA) and immune infiltration analyses were conducted to explore the potential clinical value of the FRLSG. In addition, drug sensitivity prediction was applied to identify chemotherapeutic drugs with potential therapeutic effect.
Five ferroptosis-related lncRNAs (AC004816.1, AC005532.1, LINC01357, AL355574.1 and AL049840.4) were identified to construct FRLSG, whose expression level in GC were confirmed by experimental validation. Kaplan-Meier curve and ROC curve proved the reliability and effectiveness of the FRLSG in predicting the prognosis for GC patients. Several immune-related pathways were enriched in the high-FRLSG group, and further immune infiltration analyses demonstrated the high immune infiltration status of the high-FRLSG group. In addition, 19 and 24 candidate drugs with potential therapeutic effect were identified for the high- and low-FRLSG groups, respectively.
FRLSG was an effective tool in predicting the prognosis of GC, which might help to prioritize potential therapeutics for GC patients.
胃癌（GC）是全球最具侵袭性的恶性肿瘤之一。铁死亡是一种铁依赖性的细胞死亡方式，已被证明与肿瘤进展密切相关。在本研究中，我们旨在构建一个与铁死亡相关的长链非编码 RNA（lncRNA）特征，以预测 GC 患者的预后，并探索潜在的治疗方法。
通过单因素 Cox 回归、LASSO 算法和多因素 Cox 回归构建 GC 患者的铁死亡相关 lncRNA 特征（FRLSG）。Kaplan-Meier 分析、受试者工作特征曲线和风险评分图用于验证 FRLSG 的预测能力。基因集富集分析（GSEA）和免疫浸润分析用于探讨 FRLSG 的潜在临床价值。此外，还进行了药物敏感性预测，以确定具有潜在治疗效果的化疗药物。
确定了 5 个与铁死亡相关的 lncRNA（AC004816.1、AC005532.1、LINC01357、AL355574.1 和 AL049840.4）来构建 FRLSG，并通过实验验证了其在 GC 中的表达水平。Kaplan-Meier 曲线和 ROC 曲线证明了 FRLSG 预测 GC 患者预后的可靠性和有效性。高-FRLSG 组富集了几个与免疫相关的通路，进一步的免疫浸润分析表明高-FRLSG 组具有较高的免疫浸润状态。此外，还分别为高-FRLSG 组和低-FRLSG 组确定了 19 种和 24 种候选潜在治疗药物。
FRLSG 是预测 GC 预后的有效工具，可能有助于为 GC 患者确定潜在的治疗方法。
