Identification and validation of plasma exosomal FGL1 as an early diagnostic biomarker for non-small cell lung cancer

Objective Non-small cell lung carcinoma (NSCLC) is the leading cause of cancer-related death worldwide. Nevertheless, reliable and effective biomarkers for early diagnosis of NSCLC are currently unavailable. In recent years, increasing studies suggest that exosomes have a great promise to serve as novel biomarkers in liquid biopsy. This study aimed to identify the plasma exosomal biomarkers for NSCLC early detection. Methods We utilized label-free quantification to conduct differential proteomic analysis of plasma exosomes between patients with early stage NSCLC and healthy control subjects. NSCLC samples were divided into lung squamous carcinoma (LUSC) group and lung adenocarcinoma (LUAD) group. GO and KEGG pathway analysis of differentially expressed proteins (DEPs) were performed for every module by DAVID. Furthermore, the protein with the most significant difference was validated using Enzyme-linked immunosorbent assay (ELISA) at levels of plasma exosomes and plasma respectively. Finally, the receiver operating characteristic (ROC) analysis was used to evaluate the efficiency of plasma exosomal FGL1 for early diagnosis of NSCLC. Results Compared with Control group, 65 and 53 DEPs were identified in LUSC group and LUAD group respectively. Bioinformatics analysis indicated that the DEPs were mainly involved in multiple biological functions and cancer-related pathways. Furthermore, we identified 34 proteins with similar expression trends between the LUSC and LUAD groups. Among these proteins, Fibrinogen like protein 1 (FGL1) was selected as a candidate plasma exosomal biomarker for subsequent validation since it was upregulated by more than 5-fold in NSCLC group. ELISA results showed that the plasma exosomal FGL1 concentration were significantly higher in NSCLC patients than in Control samples, which were consistent with the trend of proteomics results. Moreover, receiver operating characteristic (ROC) analysis of plasma exosomal FGL1 demonstrated that the diagnostic AUC, sensitivity, and specificity were 0.866, 82.50%, and 76.25% respectively. However, ROC analysis of plasma FGL1 revealed that the diagnostic AUC, sensitivity, and specificity were 0.757, 56.88%, and 83.75% individually. The diagnostic efficiency of plasma exosomal FGL1 was higher than plasma FGL1 in diagnosing early stage NSCLC patients. Conclusion This study provided a reference proteome map of plasma exosomes in LUSC and LUAD patients. Plasma exosomal FGL1 has the potential to become a promising biomarker for early diagnosis of NSCLC.