Integrating multiple machine learning methods to construct glutamine metabolism-related signatures in lung adenocarcinoma

Frontiers in Endocrinology

Endocrinology

Shengbin Pei¹  Jiaheng Xie²  Zhangzuo Li³  Qi Wang⁴  Zhijia Xia⁵  Leilei Wu⁶  Mingjun Du⁷  Haoran Lin⁷  Pengpeng Zhang⁷  Xufeng Huang⁸ 

[1] Department of Breast Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China;Department of Burns and Plastic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China;Department of Cell Biology, School of Medicine, Jiangsu University, Zhenjiang, China;Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, China;Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, Munich, Germany;Department of Radiation Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China;Department of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China;Faculty of Dentistry, University of Debrecen, Debrecen, Hungary;

关键词: lung adenocarcinoma;    glutamine;    signature;    prognosis;    machine learning;   

DOI  :  10.3389/fendo.2023.1196372

 received in 2023-03-29, accepted in 2023-05-04,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundGlutamine metabolism (GM) is known to play a critical role in cancer development, including in lung adenocarcinoma (LUAD), although the exact contribution of GM to LUAD remains incompletely understood. In this study, we aimed to discover new targets for the treatment of LUAD patients by using machine learning algorithms to establish prognostic models based on GM-related genes (GMRGs).MethodsWe used the AUCell and WGCNA algorithms, along with single-cell and bulk RNA-seq data, to identify the most prominent GMRGs associated with LUAD. Multiple machine learning algorithms were employed to develop risk models with optimal predictive performance. We validated our models using multiple external datasets and investigated disparities in the tumor microenvironment (TME), mutation landscape, enriched pathways, and response to immunotherapy across various risk groups. Additionally, we conducted in vitro and in vivo experiments to confirm the role of LGALS3 in LUAD.ResultsWe identified 173 GMRGs strongly associated with GM activity and selected the Random Survival Forest (RSF) and Supervised Principal Components (SuperPC) methods to develop a prognostic model. Our model’s performance was validated using multiple external datasets. Our analysis revealed that the low-risk group had higher immune cell infiltration and increased expression of immune checkpoints, indicating that this group may be more receptive to immunotherapy. Moreover, our experimental results confirmed that LGALS3 promoted the proliferation, invasion, and migration of LUAD cells.ConclusionOur study established a prognostic model based on GMRGs that can predict the effectiveness of immunotherapy and provide novel approaches for the treatment of LUAD. Our findings also suggest that LGALS3 may be a potential therapeutic target for LUAD.

【 授权许可】

Unknown   
Copyright © 2023 Zhang, Pei, Wu, Xia, Wang, Huang, Li, Xie, Du and Lin