Mao Guoliang, Xu Wuqin, Jamil Muhammad, Zhang Wei, Jiao Nanlin, Liu Yinhua
Department of Pathology, Wannan Medical College First Affiliated Hospital, Yijishan Hospital, Wuhu, China.
PARC Arid Zone Research Center, Dera Ismail Khan, Pakistan.
Curr Pharm Biotechnol. 2025;26(3):411-427. doi: 10.2174/0113892010293337240312051931.
Lung Adenocarcinoma (LUAD), a common and aggressive form of lung cancer, poses significant treatment challenges due to its low survival rates.
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.
To accomplish the defined goals, a comprehensive methodology incorporating both 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.
RESULTS & 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.
Therapeutic targeting of these genes using specific drugs holds great promise for revolutionizing drug discovery and improving the overall survival of LUAD patients.
肺腺癌（LUAD）是一种常见且侵袭性强的肺癌形式，因其低生存率而带来重大治疗挑战。
为了更好地理解铁死亡驱动基因在LUAD中的作用，本研究旨在探索它们的诊断和预后意义，以及它们对LUAD治疗方法和肿瘤免疫功能的影响。
为实现既定目标，采用了结合干实验和湿实验的综合方法。对从FerrDB数据库获得的总共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技术检测了233个基因的表达谱。其中，TP53、KRAS、PTEN和HRAS被确定为具有显著差异表达的枢纽基因。值得注意的是，在LUAD样本中，TP53、KRAS和HRAS在mRNA和蛋白质水平均表现出显著上调，而PTEN则表现出显著下调。枢纽基因的失调与LUAD患者较差的总生存率进一步相关。此外，靶向亚硫酸氢盐测序（bisulfite-seq）分析揭示了与枢纽基因失调相关的异常启动子甲基化模式。
此外，发现枢纽基因参与多种致癌途径，突出了它们在LUAD肿瘤发生中的作用。通过利用铁死亡驱动枢纽基因（TP53、KRAS、PTEN和HRAS）的诊断和预后潜力，可以在理解和管理LUAD发病机制方面取得重大进展。
使用特定药物对这些基因进行治疗靶向有望彻底改变药物发现并提高LUAD患者的总生存率。
