CPB2 is a potential biomarker for EGFR-T790M resistance gene mutations in advanced lung adenocarcinoma
Objective To verify the presence of epidermal growth factor receptor(EGFR)-T790M resistance mutant biomarkers in patients with advanced lung adenocarcinoma using the quantitative proteomic approach known as parallel reaction monitoring(PRM).Methods Forty-four advanced lung adenocarcinoma patients with EGFR 19del or EGFR 21 L858R mutation and treated with EGFR-ty-rosine kinase inhibitor(TKI)gefitinib at the Affiliated Tumor Hospital of Xinjiang Medical University from January 2018 to December 2018 were included in this study.Tissue biopsies were conducted after disease progression.Next generation sequencing(NGS)was employed to identify EGFR-T790M mutation in 24 patients and no EGFR-T790M mutation in 20 patients.Forty-four patients'serum proteins were ex-tracted and evaluated using SDS-PAGE.High-quality serum protein samples were obtained from 10 patients with EGFR-T790M mutation and 10 without EGFR-T790M mutation.These high-quality samples were individually digested with serine protease enzymes and then an-alyzed using nanometer liquid chromatography-tandem mass spectrometry(nanoLC-MS/MS)via the PRM method.The resulting data were analyzed using Skyline software to identify the differentially expressed proteins associated with EGFR-T790M mutation.The genes were assigned to the nodes of the Gene Ontology(GO)database,and functional enrichment analysis was conducted.The expression patterns of the differentially expressed proteins were visualized using the mapping module provided by the Kyoto Encyclopaedia of Genes and Genomes(KEGG)database.The STRING database was utilized to construct protein-protein interaction(PPI)networks of the differentially expressed proteins in order to identify key differentially expressed proteins.Results The PRM technique successfully identified 14 distinct proteins that were differently expressed in advanced lung adenocarcinoma with EGFR-T790M mutation.The GO enrichment analysis revealed that the 14 differentially expressed proteins primarily belonged to the extracellular region in terms of their involvement in cellular components.In terms of their molecular functions,these proteins were mainly involved in antigen-binding,peptidase activity acting on L-amino acid peptides,and immunoglobulin receptor binding.KEGG enrichment pathway analysis indicated that the differentially expressed proteins involved in the complement and coagulation cascade response had the highest enrichment index.The proteins that showed differential ex-pression in this pathway were coagulation factor X(F10),F9,plasminogen(PLG),and carboxypeptidase B2(CPB2),with F10 upregulated and the others downregulated.PPI network analysis revealed that CBP2 played a crucial role as a central node among the differentially expressed proteins.Conclusions CBP2 is a potential biomarker indicating the presence of the EGFR-T790M resistance mutation in ad-vanced lung adenocarcinoma.
advanced lung adenocarcinomaEGFR-T790Mproteomicsdifferential protein
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