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Cell ; 182(1): 245-261.e17, 2020 07 09.
Article in English | MEDLINE | ID: mdl-32649877

ABSTRACT

Genomic studies of lung adenocarcinoma (LUAD) have advanced our understanding of the disease's biology and accelerated targeted therapy. However, the proteomic characteristics of LUAD remain poorly understood. We carried out a comprehensive proteomics analysis of 103 cases of LUAD in Chinese patients. Integrative analysis of proteome, phosphoproteome, transcriptome, and whole-exome sequencing data revealed cancer-associated characteristics, such as tumor-associated protein variants, distinct proteomics features, and clinical outcomes in patients at an early stage or with EGFR and TP53 mutations. Proteome-based stratification of LUAD revealed three subtypes (S-I, S-II, and S-III) related to different clinical and molecular features. Further, we nominated potential drug targets and validated the plasma protein level of HSP 90ß as a potential prognostic biomarker for LUAD in an independent cohort. Our integrative proteomics analysis enables a more comprehensive understanding of the molecular landscape of LUAD and offers an opportunity for more precise diagnosis and treatment.


Subject(s)
Adenocarcinoma of Lung/metabolism , Lung Neoplasms/metabolism , Proteomics , Adenocarcinoma of Lung/genetics , Asian People/genetics , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Drug Delivery Systems , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/genetics , Male , Middle Aged , Mutation/genetics , Neoplasm Staging , Phosphoproteins/metabolism , Principal Component Analysis , Prognosis , Proteome/metabolism , Treatment Outcome , Tumor Suppressor Protein p53/genetics
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