Exploring the Diagnostic and Prognostic Predictive Values of Ferroptosis-related Markers in Lung Adenocarcinoma.

IF 2.2 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Guoliang Mao, Wuqin Xu, Muhammad Jamil, Wei Zhang, Nanlin Jiao, Yinhua Liu
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引用次数: 0

Abstract

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.

Methods: 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.

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.

Conclusion: Therapeutic targeting of these genes using specific drugs holds great promise for revolutionizing drug discovery and improving the overall survival of LUAD patients.

探索肺腺癌铁蛋白沉积相关标记物的诊断和预后预测价值
背景:肺腺癌(LUAD)是一种常见的侵袭性肺癌:目的:为了更好地了解铁突变驱动基因在肺腺癌中的作用,本研究旨在探索它们在肺腺癌中的诊断和预后意义,以及它们对治疗方法和肿瘤免疫功能的影响:为了实现既定目标,我们采用了一种结合了硅学和湿实验室实验的综合方法。对从FerrDB数据库中获得的共233个铁变态反应驱动基因进行了综合分析。利用各种 TCGA 数据库和 RT-qPCR 技术,研究了 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表现出显著的上调,而PTEN在mRNA和蛋白水平均表现出显著的下调。枢纽基因的失调与 LUAD 患者的总生存率低进一步相关。此外,靶向亚硫酸氢盐测序(bisulfite-sequencing,bisulfite-seq)分析显示,异常启动子甲基化模式与枢纽基因的失调有关:此外,研究还发现枢纽基因参与了多种致癌通路,这突显了它们在LUAD肿瘤发生过程中的参与作用。通过利用铁突变驱动中心基因(TP53、KRAS、PTEN 和 HRAS)的诊断和预后潜力,可以在了解和管理 LUAD 发病机制方面取得重大进展:结论:使用特异性药物对这些基因进行靶向治疗,有望彻底改变药物研发,提高 LUAD 患者的总体生存率。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Current pharmaceutical biotechnology
Current pharmaceutical biotechnology 医学-生化与分子生物学
CiteScore
5.60
自引率
3.60%
发文量
203
审稿时长
6 months
期刊介绍: Current Pharmaceutical Biotechnology aims to cover all the latest and outstanding developments in Pharmaceutical Biotechnology. Each issue of the journal includes timely in-depth reviews, original research articles and letters written by leaders in the field, covering a range of current topics in scientific areas of Pharmaceutical Biotechnology. Invited and unsolicited review articles are welcome. The journal encourages contributions describing research at the interface of drug discovery and pharmacological applications, involving in vitro investigations and pre-clinical or clinical studies. Scientific areas within the scope of the journal include pharmaceutical chemistry, biochemistry and genetics, molecular and cellular biology, and polymer and materials sciences as they relate to pharmaceutical science and biotechnology. In addition, the journal also considers comprehensive studies and research advances pertaining food chemistry with pharmaceutical implication. Areas of interest include: DNA/protein engineering and processing Synthetic biotechnology Omics (genomics, proteomics, metabolomics and systems biology) Therapeutic biotechnology (gene therapy, peptide inhibitors, enzymes) Drug delivery and targeting Nanobiotechnology Molecular pharmaceutics and molecular pharmacology Analytical biotechnology (biosensing, advanced technology for detection of bioanalytes) Pharmacokinetics and pharmacodynamics Applied Microbiology Bioinformatics (computational biopharmaceutics and modeling) Environmental biotechnology Regenerative medicine (stem cells, tissue engineering and biomaterials) Translational immunology (cell therapies, antibody engineering, xenotransplantation) Industrial bioprocesses for drug production and development Biosafety Biotech ethics Special Issues devoted to crucial topics, providing the latest comprehensive information on cutting-edge areas of research and technological advances, are welcome. Current Pharmaceutical Biotechnology is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments.
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