Role of immune cell infiltration and small molecule drugs in adhesive capsulitis: Novel exploration based on bioinformatics analyses

Hailong Liu; Baoxi Yu; Zengfa Deng; Hang Zhao; Anyu Zeng; Ruiyun Li; Ming Fu

doi:10.3389/fimmu.2023.1075395

Role of immune cell infiltration and small molecule drugs in adhesive capsulitis: Novel exploration based on bioinformatics analyses

Front Immunol. 2023 Feb 9:14:1075395. doi: 10.3389/fimmu.2023.1075395. eCollection 2023.

Authors

Hailong Liu^{1

2}, Baoxi Yu^{1

2}, Zengfa Deng^{1

2}, Hang Zhao³, Anyu Zeng^{1

2}, Ruiyun Li⁴, Ming Fu^{1

2}

Affiliations

¹ Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
² Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
³ China-Japan Friendship School of Clinical Medicine, Peking University, Beijing, China.
⁴ Department of Anesthesiology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.

Abstract

Background: Adhesive capsulitis (AC) is a type of arthritis that causes shoulder joint pain, stiffness, and limited mobility. The pathogenesis of AC is still controversial. This study aims to explore the role of immune related factors in the occurrence and development of AC.

Methods: The AC dataset was downloaded from Gene Expression Omnibus (GEO) data repository. Differentially expressed immune-related genes (DEIRGs) were obtained based on R package "DESeq2" and Immport database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to explore the functional correlation of DEIRGs. MCC method and Least Absolute Shrinkage and Selection Operator (LASSO) regression were conducted to identify the hub genes. The immune cell infiltration in shoulder joint capsule between AC and control was evaluated by CIBERSORTx, and the relationship between hub genes and infiltrating immune cells was analyzed by Spearman's rank correlation. Finally, potential small molecule drugs for AC were screened by the Connectivity Map database (CMap) and further verified by molecular docking.

Results: A total of 137 DEIRGs and eight significantly different types of infiltrating immune cells (M0 macrophages, M1 macrophages, regulatory T cells, Tfh cells, monocytes, activated NK cells, memory resting CD4+T cells and resting dendritic cells) were screened between AC and control tissues. MMP9, FOS, SOCS3, and EGF were identified as potential targets for AC. MMP9 was negatively correlated with memory resting CD4+T cells and activated NK cells, but positively correlated with M0 macrophages. SOCS3 was positively correlated with M1 macrophages. FOS was positively correlated with M1 macrophages. EGF was positively correlated with monocytes. Additionally, dactolisib (ranked first) was identified as a potential small-molecule drug for the targeted therapy of AC.

Conclusions: This is the first study on immune cell infiltration analysis in AC, and these findings may provide a new idea for the diagnosis and treatment of AC.

Keywords: CIBERSORTx; adhesive capsulitis; bioinformatics; frozen shoulder; immune infiltration; shoulder capsule.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bursitis*
Computational Biology
Epidermal Growth Factor
Humans
Matrix Metalloproteinase 9*
Molecular Docking Simulation

Substances

Matrix Metalloproteinase 9
Epidermal Growth Factor

Grants and funding

This study was supported by the National Natural Science Foundation of China (NSFC) Project (No. 81974343).