肺腺癌（LUAD）是肺癌的主要亚型。尽管LUAD的分子分类被广泛研究，但基于蛋白质组学的LUAD亚型分型仍然很少。我们提出了一种基于LUAD中500个表达变异性最大的蛋白质的表达谱的分型方法。此外，我们全面比较了LUAD亚型之间的分子和临床特征。共识聚类鉴定出三种LUAD亚型，即MtE、DrE和StE。我们通过分析两个独立的LUAD队列证明了这种分型方法的可重复性。MtE以代谢途径的高富集、高EGFR突变率、低干性、增殖、侵袭、转移和炎症标志物、有利的预后为特征；DrE以DNA修复途径的高富集、高TP53突变率和高水平的基因组不稳定、干性、增殖和肿瘤内异质性（ITH）为特征；而StE则以结缔组织相关途径的高富集、高KRAS突变率和低基因组不稳定水平为特征。蛋白质组学聚类分析鉴定出具有显著不同分子和临床特征的三个LUAD亚型。这种新型分型方法为肺腺癌的癌症生物学提供了新的视角，并在改善LUAD的临床管理方面具有潜力。© 2023. 作者，由西班牙肿瘤学学会（FESEO）独家授权使用。

Lung adenocarcinoma (LUAD) is a predominant subtype of lung cancer. Although molecular classification of LUAD has been widely explored, proteomics-based subtyping of LUAD remains scarce.We proposed a subtyping method for LUAD based on the expression profiles of 500 proteins with the largest expression variability across LUAD. Furthermore, we comprehensively compared molecular and clinical features among the LUAD subtypes.Consensus clustering identified three subtypes of LUAD, namely MtE, DrE, and StE. We demonstrated this subtyping method to be reproducible by analyzing two independent LUAD cohorts. MtE was characterized by high enrichment of metabolic pathways, high EGFR mutation rate, low stemness, proliferation, invasion, metastasis and inflammation signatures, favorable prognosis; DrE was characterized by high enrichment of DNA repair pathways, high TP53 mutation rate, and high levels of genomic instability, stemness, proliferation, and intratumor heterogeneity (ITH); and StE was characterized by high enrichment of stroma-related pathways, high KRAS mutation rate, and low levels of genomic instability.The proteomics-based clustering analysis identified three LUAD subtypes with significantly different molecular and clinical properties. The novel subtyping method offers new perspectives on the cancer biology and holds promise in improving the clinical management of LUAD.© 2023. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).