Screening and identification of biomarkers in tumor-educated platelets for non-small cell lung cancer

BACKGROUND: Platelets, a crucial source of liquid biopsy samples, play a significant role in the progression of various malignancies, including non-small cell lung cancer (NSCLC). However, specific biomarkers for early-stage NSCLC have not yet been identified. In this study, we employed bioinformatics approaches to identify differentially expressed genes (DEGs) in tumor-educated platelets (TEPs) from NSCLC. Subsequently, we validated these genes using specimens from patients with early-stage lung cancer, highlighting their potential as biomarkers for NSCLC. METHODS: We analyzed the platelet mRNA expression profile microarray dataset GSE89843, which comprises samples from NSCLC patients and healthy controls. Utilizing R software, we eliminated batch effects and identified DEGs. NSCLC-associated module genes were identified via weighted gene co-expression network analysis (WGCNA). Enrichment analysis was performed using R-based tools, and protein-protein interaction (PPI) analysis was conducted to identify key DEGs. Finally, RT-qPCR validation was performed to assess the differential expression of selected genes in platelet total RNA between early-stage NSCLC patients and healthy controls. RESULTS: Initially, we analyzed the RNA sequencing data from dataset GSE89843, which contains 779 platelet samples, and identified 532 DEGs (72 upregulated and 460 downregulated). Among these DEGs, seven key genes were identified: HSP90AB1, NPM1, CD44, HSPA4, CD74, SEC31A, and EIF2S1. Notably, CD44 served as the interaction starting point in gene association networks. Meanwhile, HSP90AB1, NPM1, and CD74 exhibited low expression levels in NSCLC. RT-qPCR validation confirmed that HSP90AB1, NPM1, CD44, and CD74 exhibited significantly downregulated expression in platelets from early-stage (I and II) NSCLC patients. CONCLUSION: Specific DEGs for NSCLC are present in platelets, including HSP90AB1, NPM1, CD44, and CD74, which may play a role in the early stages of NSCLC development. These genes exhibit a specific expression pattern, characterized by downregulation in early-stage (I and II) NSCLC, indicating their potential as biomarkers for early screening and diagnosis of NSCLC.