Identification of candidate biomarkers for severe adenovirus community-acquired pneumonia by proteomic approach

Abstract

Introduction: Worldwide, Human adenoviruses (ADV) cause a significant portion of childhood mortality. The severity of ADV Community-acquired Pneumonia (CAP) can be assessed by clinical features, but the rapid and accurate diagnostic biomarkers are still lacking. Candidate biomarkers for severe ADV CAP are to be screened and the different protein expression levels associated with pediatric ADV CAP may help assess the severity of ADV CAP for the pediatricians to make early intervention. Methods: In our study, serum samples from healthy controls, patients with ADV CAP, streptococcus pneumonia (SP) and respiratory syncytial virus (RSV) infection were collected. Differently expressed proteins (DEPs) were detected by iTRAQ-based mass spectrometry. Gene Ontology and Pathway Enrichment analysis of DEPs were performed by Cytoscape. The protein interaction network for the identified proteins was constructed by String. Results: The results showed that 119 DEPs in mild ADV CAP and 148 DEPs in severe ADV CAP were identified, compared with healthy children. Four proteins (Protein S100-A9 (S100A9), Protein S100-A8 (S100A8), Leucine aminopeptidase III (LAP3), and Apolipoprotein A-IV(APOA4)) were validated by Western blot, and results indicated that the expression levels of these four proteins were consistent with the proteomic analysis. LAP3 was the most significantly up-regulated protein in severe ADV CAP compared to mild group. In addition, LAP3 was the most significantly up-regulated protein in severe ADV CAP comparing with SP CAP infection and RSV CAP infection. Conclusion: Our findings identified LAP3 protein as a potential diagnostic biomarker which can assess the severity of ADV CAP.

Keywords

• Adenoviruses
• Pneumonia
• LAP3 protein
• Biomarker