WDR43 is a potential diagnostic biomarker and therapeutic target for osteoarthritis complicated with Parkinson's disease

Hongquan Heng; Jie Liu; Mingwei Hu; Dazhuang Li; Wenxing Su; Jian Li

doi:10.3389/fncel.2022.1013745

WDR43 is a potential diagnostic biomarker and therapeutic target for osteoarthritis complicated with Parkinson's disease

Front Cell Neurosci. 2022 Nov 7:16:1013745. doi: 10.3389/fncel.2022.1013745. eCollection 2022.

Authors

Hongquan Heng^{1

2}, Jie Liu^{3

4}, Mingwei Hu⁵, Dazhuang Li⁴, Wenxing Su², Jian Li¹

Affiliations

¹ Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, China.
² Department of Plastic and Burn Surgery, The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu, China.
³ Department of Orthopedics, Liyang People's Hospital, Liyang, China.
⁴ Department of Orthopedics, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China.
⁵ Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Abstract

Osteoarthritis (OA) and Parkinson's disease (PD) are on the rise and greatly impact the quality of individuals' lives. Although accumulating evidence indicates a relationship between OA and PD, the particular interactions connecting the two diseases have not been thoroughly examined. Therefore, this study explored the association through genetic characterization and functional enrichment. Four datasets (GSE55235, GSE12021, GSE7621, and GSE42966) were chosen for assessment and validation from the Gene Expression Omnibus (GEO) database. Weighted Gene Co-Expression Network Analysis (WGCNA) was implemented to determine the most relevant genes for clinical features. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were carried out to explore the biological processes of common genes, and to display the interrelationships between common genes, the STRING database and the application Molecular Complex Detection Algorithm (MCODE) of Cytoscape software were leveraged to get hub genes. By intersecting the common genes with the differentially expressed genes (DEGs) acquired from GSE12021 and GSE42966, the hub genes were identified. Finally, we validated the diagnostic efficacy of hub genes and explored their correlation with 22 immune infiltrating cells. As a consequence, we discovered 71 common genes, most of which were functionally enriched in antigen processing and presentation, mitochondrial translation, the mRNA surveillance pathway, and nucleocytoplasmic transport. Furthermore, WDR43 was found by intersecting eight hub genes with 28 DEGs from the two validation datasets. Receiver Operating Characteristic (ROC) implied the diagnostic role of WDR43 in OA and PD. Immune infiltration research revealed that T-cell regulatory (Tregs), monocytes, and mast cells resting were associated with the pathogenesis of OA and PD. WDR43 may provide key insights into the relationship between OA and PD.

Keywords: Parkinson’s disease; hub gene; immune cell infiltration; osteoarthritis; weighted gene co-expression network analysis.