Cerebrospinal fluid exosomal protein alterations via proteomic analysis of NSCLC with leptomeningeal carcinomatosis.

Purpose: Leptomeningeal carcinomatosis (LC) is a rare complication of non-small cell lung cancer (NSCLC) with highly mortality. Cerebrospinal fluid (CSF) as a special kind of tumor microenvironment (TME) better represents alterations than plasma. However, the clinical value of protein profiles of exosome in CSF as liquid biopsy remains unclear.

Methods: In this study, CSF samples of NSCLC patients with (LC group) or without (NSCLC group) LC were collected and compared to patients without tumors (normal group). CSF exosomes were isolated by ultracentrifugation and protein profiles were performed by label-free proteomics. Differentially expressed proteins (DEPs) were detected by bioinformatics tools and verified by parallel reaction monitoring (PRM).

Results: A total of 814 proteins were detected. Bioinformatics analysis revealed their shared function in the complement activation, extracellular region, and complement and coagulation cascades. Between LC and NSCLC group, 72 DEPs were found among which FN1 demonstrated the highest betweenness centrality (BC) after protein-protein interaction network analysis.

Conclusion: We investigated the application of label free and PRM based proteomics to detect key proteins related to LC. FN1 may serve as potential indicator to classify LC and NSCLC. Extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT) are important in the process of LC. These data is promising for early prediction and diagnosis of LC.