Background: Lung Adenocarcinoma (LUAD), a common and aggressive form of lung cancer, poses significant treatment challenges due to its low survival rates. Aim: To better understand the role of ferroptosis driver genes in LUAD, this study aimed to explore their diagnostic and prognostic significance, as well as their impact on treatment approaches and tumor immune function in LUAD. Method: To accomplish the defined goals, a comprehensive methodology incorporating both in silico and wet lab experiments was employed. A comprehensive analysis was conducted on a total of 233 ferroptosis driver genes obtained from the FerrDB database. Utilizing various TCGA databases and the RT-qPCR technique, the expression profiles of 233 genes were examined. Among them, TP53, KRAS, PTEN, and HRAS were identified as hub genes with significant differential expression. Notably, TP53, KRAS, and HRAS exhibited substantial up-regulation, while PTEN demonstrated significant down-regulation at both the mRNA and protein levels in LUAD samples. The dysregulation of hub genes was further associated with poor overall survival in LUAD patients. Additionally, targeted bisulfite-sequencing (bisulfite-seq) analysis revealed aberrant promoter methylation patterns linked to the dysregulation of hub genes. Result & Discussion: Furthermore, hub genes were found to participate in diverse oncogenic pathways, highlighting their involvement in LUAD tumorigenesis. By leveraging the diagnostic and prognostic potential of ferroptosis driver hub genes (TP53, KRAS, PTEN, and HRAS), significant advancements can be made in the understanding and management of LUAD pathogenesis. Conclusion: Therapeutic targeting of these genes using specific drugs holds great promise for revolutionizing drug discovery and improving the overall survival of LUAD patients.

中文翻译：

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探索铁死亡相关标志物在肺腺癌中的诊断和预后预测价值

背景：肺腺癌（LUAD）是一种常见且具有侵袭性的肺癌，由于其生存率低，给治疗带来了巨大的挑战。目的：为了更好地了解铁死亡驱动基因在 LUAD 中的作用，本研究旨在探讨其诊断和预后意义，以及它们对 LUAD 治疗方法和肿瘤免疫功能的影响。方法：为了实现既定目标，采用了结合计算机模拟和湿实验室实验的综合方法。对FerrDB数据库中获得的总共233个铁死亡驱动基因进行了全面分析。利用各种TCGA数据库和RT-qPCR技术，检查了233个基因的表达谱。其中TP53、KRAS、PTEN、HRAS被确定为差异表达显着的枢纽基因。值得注意的是，在 LUAD 样本中，TP53、KRAS 和 HRAS 表现出显着上调，而 PTEN 在 mRNA 和蛋白质水平上表现出显着下调。 Hub 基因的失调进一步与 LUAD 患者较差的总生存率相关。此外，靶向亚硫酸氢盐测序（bisulfite-seq）分析揭示了与中枢基因失调相关的异常启动子甲基化模式。结果与讨论：此外，发现 hub 基因参与多种致癌途径，强调它们参与 LUAD 肿瘤发生。通过利用铁死亡驱动中枢基因（TP53、KRAS、PTEN 和 HRAS）的诊断和预后潜力，可以在 LUAD 发病机制的理解和管理方面取得重大进展。结论：使用特定药物对这些基因进行治疗，有望彻底改变药物发现并提高 LUAD 患者的总体生存率。