Identification and Analysis of Amino Acid Metabolism-Related Subtypes in Lung Adenocarcinoma.

Yifan Zhou, Qiangchang Lu
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Abstract

Background: We aimed to explore the role of Amino acid metabolism (AAM) and identify biomarkers for prognosis management and treatment of lung adenocarcinoma. Methods: Differentially expressed genes (DEGs) associated with AAM in lung adenocarcinoma were selected from public databases. Samples were clustered into varying subtypes using ConsensusClusterPlus based on gene levels. Survival analysis was conducted using a survival package, and immune analysis was performed using ssGSEA and ESTIMATE. Enrichment analysis was performed using GSEA, and a protein-protein interaction network of DEGs between subgroups was established through STRING. Hub genes were screened and verified using survival analysis, and drug sensitivity prediction was performed. Results: 163 DEGs associated with AAM in lung adenocarcinoma were obtained, and two AAM-associated subtypes were identified. Cluster1 showed higher survival rates and immune levels compared with cluster2. The two subtypes were mainly enriched in immune-related signaling pathways such as B cell receptor, Jak-Stat, and natural killer cell-mediated cytotoxicity. Additionally, the mutation landscape between the two groups was significantly different. F2, AHSG, and APOA1 were key hub genes that significantly affected the prognosis differences between the two subtypes. Cluster2 showed higher sensitivity to drugs such as Mithramycin, Depsipeptide, and Actinomycin than cluster1. Conclusion: This study identified two AAM-associated gene subtypes and their biomarkers and predicted the immune status and drug treatment sensitivity of varying subtypes. The results are instructive in the clinical treatment of lung adenocarcinoma.

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肺腺癌中氨基酸代谢相关亚型的鉴定与分析。
背景:我们旨在探讨氨基酸代谢(AAM)在肺腺癌预后管理和治疗中的作用,并确定生物标志物。方法:从公开数据库中筛选与肺腺癌AAM相关的差异表达基因(DEGs)。使用ConsensusClusterPlus基于基因水平将样本聚类成不同的亚型。使用生存包进行生存分析,使用ssGSEA和ESTIMATE进行免疫分析。通过GSEA进行富集分析,并通过STRING建立亚组间DEGs蛋白相互作用网络。通过生存分析筛选和验证Hub基因,并进行药物敏感性预测。结果:在肺腺癌中获得163个与AAM相关的deg,并鉴定出2个AAM相关亚型。与cluster2相比,Cluster1的存活率和免疫水平更高。这两种亚型主要富集于免疫相关信号通路,如B细胞受体、Jak-Stat和自然杀伤细胞介导的细胞毒性。此外,两组之间的突变格局也有显著差异。F2、AHSG和APOA1是影响两亚型预后差异的关键枢纽基因。Cluster2对米霉素、沈肽、放线菌素等药物的敏感性高于cluster1。结论:本研究确定了两种aam相关基因亚型及其生物标志物,并预测了不同亚型的免疫状态和药物治疗敏感性。结果对肺腺癌的临床治疗具有指导意义。
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来源期刊
CiteScore
5.30
自引率
3.60%
发文量
145
审稿时长
2 months
期刊介绍: The American Journal of Physiology-Regulatory, Integrative and Comparative Physiology publishes original investigations that illuminate normal or abnormal regulation and integration of physiological mechanisms at all levels of biological organization, ranging from molecules to humans, including clinical investigations. Major areas of emphasis include regulation in genetically modified animals; model organisms; development and tissue plasticity; neurohumoral control of circulation and hypertension; local control of circulation; cardiac and renal integration; thirst and volume, electrolyte homeostasis; glucose homeostasis and energy balance; appetite and obesity; inflammation and cytokines; integrative physiology of pregnancy-parturition-lactation; and thermoregulation and adaptations to exercise and environmental stress.
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