Plasma proteome analysis and validation of patients with community-acquired pneumonia: A cohort study
Lili Zhao1, Wenjie Bian1, Ying Shang1
1Department of Respiratory and Critical Care Medicine, Peking University People's Hospital, Beijing, China.
Purpose:
This study aimed to investigate the diagnostic potential of plasma biomarkers of community-acquired pneumonia (CAP) and their severity grading.
Experimental Design:
Plasma proteomes from cohort I (n = 32) with CAP were analyzed by data-independent acquisition mass spectrometry (MS). MetaboAnalyst 5.0 was used to statistically evaluate significant differences in proteins from different samples, and demographic and clinical data were recorded for all enrolled patients. Cohort II (n = 80) was used to validate candidate biomarkers. Plasma protein levels were determined using quantitative enzyme-linked immunosorbent assay (ELISA). Correlations were assessed using Pearson's correlation coefficient. A receiver operating characteristic curve was used to verify the association between the variables, CAP diagnosis, and prognosis.
Results:
121 differentially expressed proteins (DEPs) were obtained between CAP and controls. These DEPs were mainly aggregated in pathways of phagosome(hsa04145) and complement and coagulation cascades (hsa04610). No significant differential proteins were detected in bacterial, viral, and mixed infection groups. The plasma levels of fetuin-A, alpha-1-antichymotrypsin (AACT), α1-acid glycoprotein (A1AG), and S100A8/S100A9 heterodimers detected by ELISA were consistent with those of MS. AACT, A1AG, S100A8/S100A9 heterodimer, and fetuin-A can potentially be used as diagnostic predictors, and fetuin-A and AACT are potential predictors of SCAP.
Conclusions And Clinical Relevance:
Plasma protein profiling can successfully identify potential biomarkers for CAP diagnosis and disease severity assessment. These biomarkers should be further studied for their clinical application.
Insights
Plasma biomarkers show promise for diagnosing community-acquired pneumonia (CAP) and assessing its severity. Fetuin-A and alpha-1-antichymotrypsin (AACT) may predict severe CAP.
Area of Science:
- Biochemistry
- Proteomics
- Clinical Diagnostics
Background:
- Community-acquired pneumonia (CAP) poses a significant global health challenge.
- Accurate and timely diagnosis of CAP and its severity is crucial for effective treatment.
- Current diagnostic methods may lack specificity and sensitivity, necessitating novel biomarkers.
Purpose of the Study:
- To identify and validate plasma protein biomarkers for the diagnosis of CAP.
- To investigate the potential of these biomarkers in grading CAP severity.
Main Methods:
- Plasma proteomic analysis using data-independent acquisition mass spectrometry (MS) in cohort I (n=32).
- Statistical evaluation of differentially expressed proteins (DEPs) using MetaboAnalyst 5.0.
- Validation of candidate biomarkers in cohort II (n=80) using quantitative enzyme-linked immunosorbent assay (ELISA).
- Correlation and receiver operating characteristic (ROC) curve analyses for diagnostic and prognostic assessment.
Main Results:
- 121 DEPs were identified between CAP patients and controls, primarily involved in phagosome and complement/coagulation pathways.
- Plasma levels of fetuin-A, alpha-1-antichymotrypsin (AACT), α1-acid glycoprotein (A1AG), and S100A8/S100A9 heterodimers correlated between MS and ELISA.
- AACT, A1AG, S100A8/S100A9, and fetuin-A showed potential as diagnostic predictors.
- Fetuin-A and AACT emerged as potential predictors for severe CAP (SCAP).
Conclusions:
- Plasma protein profiling is effective in identifying potential biomarkers for CAP diagnosis and severity assessment.
- The identified biomarkers, including fetuin-A and AACT, warrant further investigation for clinical utility.
- These findings contribute to the development of novel diagnostic and prognostic tools for CAP.
