CLCA1 and BPIFB1 are potential novel biomarkers for asthma: an iTRAQ analysis

J Thorac Dis. 2024 Oct 31;16(10):6955-6968. doi: 10.21037/jtd-24-1366. Epub 2024 Oct 28.

Abstract

Background: Asthma is a chronic respiratory disease that affects billions of people. Due to its diverse phenotypes and endotypes with distinct pathophysiological mechanisms, significant challenges arise in its clinical diagnosis and treatment. The discovery of potential biomarkers of asthma has significant implications for its clinical classification and precise treatment. The purpose of this study is to identify potential biomarkers for asthma, providing a foundation for its diagnosis and treatment.

Methods: We constructed an ovalbumin (OVA)-sensitized asthmatic mice model and used isobaric Tags for Relative and Absolute Quantitation (iTRAQ) labeling and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) technology to identify differentially expressed proteins (DEPs) in lung tissues. We then performed enrichment analyses of the DEPs using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, and constructed protein-protein interaction (PPI) networks.

Results: We identified 242 DEPs in the asthmatic mice model and showed that heat shock protein family A (Hsp70) member 5 (HSPA5) is a central protein in asthma. Consistent with our bioinformatics analysis, our western blot validation confirmed that the protein levels of arginase 1 (ARG1), chitinase-like protein 3 (CHIL3), chloride channel accessory 1 (CLCA1), and bactericidal/permeability-increasing protein (BPI) fold-containing family B member 1 (BPIFB1) were significantly increased in asthma group compared to the control group. Thus, we found that CLCA1 and BPIFB1 were the most promising potential biomarkers of asthma.

Conclusions: Our iTRAQ analysis and western blot verification of asthmatic mice showed that HSPA5 is a central protein in asthma, and CLCA1 and BPIFB1 are novel potential biomarkers that could play significant roles in the diagnosis and treatment of asthma.

Keywords: Asthma; BPIFB1; CLCA1; biomarkers; isobaric Tags for Relative and Absolute Quantitation (iTRAQ).