Open AccessLeptin receptor is a key gene involved in the immunopathogenesis of thyroid‐associated ophthalmopathy
Author(s) -
Chen Ziyi,
Chen Zhe,
Wang Jingya,
Zhang Meng,
Wang Xiaofei,
Cuomu Deji,
Shi Bingyin,
Wang Yue
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16605
Subject(s) - kegg , leptin receptor , gene , thyroid , medicine , leptin , gene expression , cancer research , endocrinology , biology , immunology , genetics , transcriptome , obesity
Abstract Thyroid‐associated ophthalmopathy (TAO), the most common and severe manifestation of Graves' disease (GD), is a disfiguring and potentially blinding autoimmune disease. The high relapse rate (up to 20%) and substantial side effects of glucocorticoid treatment further decrease the life quality of TAO patients. To develop novel therapies, we amid to explore the immunopathogenesis of TAO. To identify the key immune‐related genes (IRGs) in TAO, we integrated the IRG expression profiles in thyrocytes from a GD patient set (GD vs healthy control) and a TAO patient set (TAO vs GD). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein‐protein interaction (PPI) and receiver operating characteristic (ROC) curve analyses identified the leptin receptor ( LEPR ) gene as the key IRG in TAO immunopathogenesis. Gene set enrichment analysis (GSEA) suggested enrichment of the antigen presentation pathway in TAO patients with higher LEPR . Increased LEPR expression was validated in TAO orbital tissues, and weighted gene co‐expression network analysis (WGCNA) showed that cell adhesion processes were positively correlated with LEPR . Our study revealed that LEPR is a key gene in TAO immunopathogenesis and plays different roles in thyrocytes and orbital tissues. Our findings provide new insights into diagnostic and therapeutic biomarkers for TAO.