Proteome Profiling of Exosome Isolated from Non-Severe Aplastic Anemia and Myelodysplastic Syndrome-Hypoplastic Plasma

Non-severe aplastic anemia (NSAA) and myelodysplastic
syndrome-hypoplastic
(MDS-h) are common hematological disorders. Their similar clinical
symptoms and lab investigations make diagnosis challenging. To discern
their differences and facilitate diagnosis, we utilized blood exosomes
and employed a quantitative proteomics approach. Exosomes were extracted,
identified from peripheral blood plasma of 20 NSAA, 10 MDS-h patients,
and 10 healthy subjects, and then analyzed by liquid chromatography-tandem
mass spectrometry (LC-MS/MS). Subcellular localization, GO, KEGG,
and Mfuzz analyses determined differentially expressed protein (DEPs)
features. Candidate proteins were validated via parallel reaction
monitoring (PRM) analysis using plasma exosome samples from the above-mentioned
subjects. LC-MS/MS identified 62 DEPs in MDS-h and 68 in the NSAA
versus MDS-h (C/M) comparison. Functional enrichment analysis of DEPs
indicated their involvement in lipid metabolism regulation in MDS-h,
while those in C/M were related to signal transduction and immunomodulation.
Mfuzz analysis yielded four large clusters with significant differences
among the three sample groups. PRM analysis identified C4A, APOA1,
and SERPINF2, with their expression validated by ELISA in NSAA, MDS-h,
and healthy subjects. Herein, we characterized exosomal proteome profiles
of NSAA and MDS-h patients, screening, and validating valuable candidate
proteins. This work informs the differential diagnosis and mechanistic
research of the NSAA and MDS-h.