Plasma proteome profiling of high-altitude polycythemia using TMT-based quantitative proteomics approach

Area of Science:

• Proteomics
• Biochemistry
• High-altitude medicine

Background:

• High-altitude polycythemia (HAPC) is a significant health issue in high-altitude regions.
• The underlying pathogenesis of HAPC remains unclear despite extensive research.

Purpose of the Study:

• To investigate plasma proteomic changes in HAPC patients using TMT-based quantitative proteomics.
• To identify potential diagnostic biomarkers for HAPC.

Main Methods:

• Comparative quantitative proteomics analysis using TMT labeling.
• Bioinformatics analysis (GO, KEGG pathway analysis) of identified proteins.
• ELISA validation and ROC analysis for biomarker assessment.

Main Results:

• Identified 818 proteins, with 19 differentially expressed between HAPC patients and healthy controls.
• Dysregulated proteins are primarily involved in complement/coagulation cascades, inflammation, and immune response.
• A panel of five proteins (C4A, C6, CALR, MASP1, CNDP1) achieved a high AUC (0.919) for HAPC diagnosis, with CNDP1 identified as a robust biomarker.

Conclusions:

• Proteomic alterations in complement, coagulation, and immune pathways are associated with HAPC.
• A combination of plasma proteins, notably CNDP1, demonstrates significant diagnostic potential for HAPC.
• This study provides valuable proteomic data and identifies potential biomarkers for HAPC diagnosis and therapy.