Use of four genes in exosomes as biomarkers for the identification of lung adenocarcinoma and lung squamous cell carcinoma

The determination of biomarkers in the blood specific for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) is crucial for the selection of effective treatment strategies and the prediction of prognosis. The purpose of the present study was to analyze the differentially expressed genes (DEGs) in LUSC and LUAD from The Cancer Genome Atlas (TCGA) database. In order to identify the potential biomarkers for non-small cell lung cancer (NSCLC) for clinical diagnosis, bioinformatics was used to analyze the DEGs of two subtypes of NSCLC, LUAD and LUSC. Exosomes were isolated from the serum of patients with LUAD or LUSC and identified using transmission electron microscopy, nanoparticle tracking analysis and western blot analysis. A total of four differential exosomal mRNAs were selected for validation with serum samples from 70 patients with NSCLC via reverse transcription-quantitative polymerase chain reaction. Receiver operating characteristic curves were established to evaluate the clinical diagnostic value of four DEGs for patients with LUAD and LUSC. The analysis based on TCGA data revealed the DEGs in LUSC and LUAD: A total of 1,619 genes were differentially expressed in patients with LUSC and LUAD. DEGs analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that inflammation-related signaling pathways, such as complement pathways, and multiple autoimmune diseases, such as systemic lupus erythematosus and asthma were mainly enriched in LUAD. The cell cycle, Hippo signaling pathway, Rap1 signaling pathway and Wnt signaling pathway were the main signaling pathways enriched in LUSC. The combination of tumor protein P63 (TP63), keratin 5 (KRT5), CEA cell adhesion molecule 6 (CEACAM6) and surfactant protein B (SFTPB) improved the specificity and sensitivity in the diagnosis of different lung cancer subtypes. Exosomal TP63, KRT5, CEACAM6 and SFTPB mRNAs can thus be used as biomarkers to differentiate between LUSC and LUAD, and may provide a novel strategy for their differential diagnosis and treatment.