Noninvasive exosomal proteomic biosignatures, including cystatin SN, peroxiredoxin‐5, and glycoprotein VI, accurately predict chronic rhinosinusitis with nasal polyps

Background

Exosomes are secreted epithelial‐derived vesicles that contain a conserved protein array representative of their parent cell. Exosomes may be reproducibly and noninvasively purified from nasal mucus. The exosomal proteome can be quantified using SOMAscan^TM, a highly multiplexed, aptamer‐based proteomic platform. The purpose of this study was to determine whether chronic rhinosinusitis with nasal polyps (CRSwNP) has a unique predictive exosomal proteomic biosignature.

Methods

Exosomes were isolated from whole mucus sampled from control and CRSwNP patients (n = 20 per group) by differential ultracentrifugation. The SOMAscan^TM platform was used to simultaneously quantify 1310 biologically relevant human proteins. Matched tissue and whole mucus proteomes were also analyzed. Differential protein expression and discriminatory power were calculated using the unweighted pair group method with arithmetic‐mean and principal component analysis, respectively. Bioinformatic analysis was performed using Ingenuity Pathway, MetaCore, and GeneMANIA analyses.

Results

The exosomal proteome demonstrated 123 significantly (p < 0.05) differentially regulated proteins in CRSwNP relative to control. Eighty of these proteins overlapped with the matched CRSwNP tissue proteome as compared with only 4 among matched whole mucus samples. Forty‐three significantly dysregulated pathway networks overlapped between the exosomal and tissue proteome in CRSwNP as compared with only 3 among matched whole mucus samples. The best‐performing protein set (cystatin‐SN, peroxiredoxin‐5, and glycoprotein VI) achieved an area under the curve (AUC) value of up to 99%.

Conclusion

Our data contribute a significant advance in the development of a reproducible, noninvasive, serial, and quantitative "liquid biopsy" for rhinosinusitis. The exosomal proteomic approach has revealed a unique biosignature associated with CRSwNP, which outperforms whole mucus sampling, and thus provides a method of noninvasive disease detection and proposes new potential therapeutic targets.

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