AUTHOR=Wang Yucheng , Lin Xiaoli , Wang Cuili , Liu Xinyu , Wu Xiaoying , Qiu Yingying , Chen Ying , Zhou Qin , Zhao Haige , Chen Jianghua , Huang Hongfeng 

TITLE=Identification of PDCD1 as a potential biomarker in acute rejection after kidney transplantation via comprehensive bioinformatic analysis

JOURNAL=Frontiers in Immunology

VOLUME=Volume 13 - 2022

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1076546

DOI=10.3389/fimmu.2022.1076546

ISSN=1664-3224

ABSTRACT=Background: Acute rejection is a determinant of prognosis following kidney transplantation. Search for novel noninvasive biomarkers for early diagnosis and prompt treatment is essential. 
Methods: Gene microarray data was downloaded from the Gene Expression Omnibus (GEO) expression profile database, and the intersected differentially expressed genes (DEGs) were calculated. We conducted the DEGs with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The distribution of immune cell infiltration was calculated by CIBERSORT. A hub gene marker was identified by intersecting the rejection-related genes from WGCNA and a selected KEGG pathway—T cell receptor signaling pathway (hsa04660), and building a protein-protein interaction network using the STRING database and Cytoscape software. We also validated the T cell membrane protein levels using a T cell exhaustion phenotype, PD1+CD57-, via flow-cytometry analysis.
Results: A total of 1450 integrated DEGs were obtained from five datasets (GSE1563, GSE174020, GSE98320, GSE36059, GSE25902). The GO, KEGG, and immune infiltration analysis showed that AR was mainly associated with T-cell activation and various T-cell-related pathways. Other immune cells, such as B cells, Macrophages, and Dendritic cells were also associated with the progress. After utilizing the WGCNA and PPI network, PDCD1 was identified as the hub gene. The flow-cytometry analysis demonstrated that both in CD4+ and CD8+ T cells, PD1+CD57- were downregulated in the acute rejection whole blood samples.
 Conclusions: Our study illustrated that PDCD1 might be a candidate diagnostic biomarker for acute kidney transplant rejection via integrative bioinformatic analysis.