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Identification of Candidate Biomarkers in Peripheral Blood for Cardiac Allograft Rejection based on Bioinformatics
1Department of Cardiovascular Surgery, Second Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China (mainland).
Insights
Early diagnosis of cardiac allograft rejection (AR) is crucial. This study identifies seven peripheral blood biomarkers, including RPL7 and SCD5, for noninvasive AR monitoring and early detection.
Area of Science:
- Immunology
- Genomics
- Biomarker Discovery
Background:
- Cardiac allograft rejection (AR) poses significant risks, including graft dysfunction and mortality.
- Early, noninvasive diagnosis of AR is essential for improved patient outcomes.
- Peripheral blood biomarkers offer a promising avenue for early AR detection.
Purpose of the Study:
- To identify candidate biomarkers in peripheral blood for the early, noninvasive diagnosis of cardiac allograft rejection.
- To analyze gene expression profiles to find differentially expressed genes associated with AR.
- To investigate the functional pathways of identified biomarkers in the context of AR.
Main Methods:
- Utilized gene expression profile data (GSE5967) from the Gene Expression Omnibus database.
- Analyzed peripheral blood samples from cardiac allograft recipients in rejection, post-rejection, and control groups.
- Applied the limma package for differential gene expression analysis and DAVID for pathway enrichment analysis.
Main Results:
- Identified 21 up-regulated and 16 down-regulated differentially expressed genes (DEGs) between rejection and control groups.
- DEGs in rejection were enriched in translation and ribosome-related functions.
- Identified 3 up-regulated and 14 down-regulated DEGs between post-rejection and control groups, enriched in lipid biosynthesis and membrane functions.
Conclusions:
- RPL7, RPL11, RPS23, RPS25, SCD5, CSF3R, and FPR1 are predicted as candidate peripheral blood biomarkers for cardiac AR.
- Up-regulated genes (RPL7, RPS25, RPS23, RPL11) may enhance AR-related cytokine translation.
- Down-regulated genes (SCD5, CSF3R, FPR1) may impact cell membrane stability and immune cell function, warranting further validation.
Background:
Cardiac allograft rejection (AR) can cause graft dysfunction and even mortality, and an early noninvasive diagnosis of cardiac AR is required. This study aims to identify candidate biomarkers in peripheral blood for cardiac AR, which might benefit early diagnosis.
Material And Methods:
Gene expression profile (ID: GSE5967) of peripheral blood from cardiac allograft recipients was achieved from the Gene Expression Omnibus database, including 7 chips in rejection group, 7 chips in post-rejection group, and 7 chips in control group. After data preprocessing, limma package was used to screen the differentially expressed genes (DEGs) between these groups (|log2 fold change| ≥0.58, and p-value <0.05). Then, online software DAVID was utilized to study the pathways and functions involving these DEGs (p-value <0.05).
Results:
Totally, 21 up-regulated and 16 down-regulated DEGs were identified between rejection and control groups, and up-regulated DEGs were mainly enriched in bio-functions about translation and ribosome. Furthermore, 3 up-regulated and 14 down-regulated DEGs were identified between post-rejection and control groups. The down-regulated DEGs in 2 contrast groups were mainly enriched in bio-functions about lipid biosynthesis and membrane.
Conclusions:
RPL7, RPL11, RPS23, RPS25, SCD5, CSF3R, and FPR1 were predicted as candidate biomarkers in peripheral blood for monitoring cardiac AR. The up-regulation of RPL7, RPS25, RPS23, and RPL11 might promote the translation of AR-related cytokines, and the down-regulation of SCD5, CSF3R, and FPR1 might reduce the stability of cell membrane, mediating cytokines secretion and the phagocytosis of macrophages. However, further studies are required to validate these predictions.
