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.