Discrimination Between Pre- and Postcapillary Pulmonary Hypertension Using Platelet RNA.

Area of Science:

• Biomarkers
• Molecular Diagnostics
• Pulmonary Hypertension

Background:

• Accurate differentiation between precapillary and postcapillary pulmonary hypertension (PH) is essential for appropriate patient management.
• Current diagnostic methods, often requiring right heart catheterization, present challenges and limitations in discrimination.
• Existing risk scores for postcapillary PH exhibit suboptimal discriminatory power.

Purpose of the Study:

• To investigate the potential of platelet-derived RNA profiles for discriminating between precapillary and postcapillary PH.
• To identify unique RNA biomarker panels for accurate classification of PH subtypes.
• To develop a novel, potentially non-invasive method for PH diagnosis.

Main Methods:

• Whole blood platelet RNA was isolated and sequenced from 100 patients (50 precapillary PH, 50 postcapillary PH).
• Differential RNA expression analysis utilized ANOVA statistics.
• Classification models were built using a support vector machine algorithm enhanced by particle swarm optimization.

Main Results:

• A panel of 1618 distinctive platelet RNAs with differential expression levels was identified.
• The optimized RNA panel and classification algorithm achieved 100% sensitivity, 60% specificity, and 80% accuracy in an independent validation cohort (n=20).
• The model demonstrated a high area under the curve (0.95) for discriminating between precapillary and postcapillary PH.

Conclusions:

• Platelet RNA profiling, enhanced by particle swarm optimization and support vector machine algorithms, shows promise for differentiating precapillary from postcapillary PH.
• This proof-of-concept study supports the development of a blood-based diagnostic test for PH.
• Such a test could improve early diagnosis of precapillary PH and reduce the need for invasive procedures in postcapillary PH patients.