Collaborative research from scientists across China have developed a comprehensive proteomic analysis on Chinese patients with lung adenocarcinoma (LUAD).
Lung cancer is one of the most commonly diagnosed and leading cause of cancer deaths in China. In past years, progress has been made in precision medicine and the genomic study of LUAD, however, many LUAD patients lack targeted therapeutic strategies.
This recent study demonstrated the molecular characteristics of LUAD, associated clinical outcomes, as well as potential prognostic biomarkers and drug targets. A comprehensive proteomic study of LUAD would be able to meet knowledge gaps between genomic abnormality and oncogenic protein function.
The team of scientists performed integrated proteomic and phosphoproteomic analyses of tumour tissues and their paired noncancerous adjacent tissues from 103 LUAD patients. A total of 11,119 proteins and 22,564 phosphorylation sites were identified. Combination of proteomics data with clinical information and genomics data produced an extensive molecular landscape of LUAD.
Through this research it was found that epithelial-mesenchymal transition, as well as inflammatory and oncogenic signalling pathways, likely led to poor prognosis in stage I LUAD. Links between genetic alterations and proteomic characteristics were determined in patients with EGFR or TP53 mutations.
Patients with EGFR mutation displayed increased expression of TTF-1 and Napsin-A. In contrast to patients with TP53 mutations, many oncogenic pathways including DNA replication and mismatch repair showed noticeable alteration.
Researchers categorised the patients into three proteomic subtypes (S-I, S-II, S-II), with each subtype showing different molecular and clinical characteristics. Comprehensive bioinformatic analysis showed that S-I patients were associated with a cellular environment and good prognosis. In contrast, S-III patients were associated with cell proliferation and proteome stability and a poor prognosis.
The phosphoproteomic analysis further revealed activated signalling pathways and kinases in different proteomic subtypes. The integrative analysis of proteomics data and clinical data further revealed 27 potential plasma biomarkers and several drug targets for LUAD.
With new insights on the genomics of LUAD, this proteomic dataset will provide valuable information and be an essential resource to boost the development of more precise diagnosis, prognosis and therapeutic options for LUAD patients.