Bioinformatic Analysis Identifies Potentially Key Differentially Expressed Genes and Pathways in Orbital Adipose Tissues of Patients with Thyroid Eye Disease

Zhu, Fang; Yang, Luwei

doi:10.4183/aeb.2019.1

Cited by 5 publications

(7 citation statements)

References 43 publications

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“…Gopinath et al [3] demonstrated that cardiac calsequestrin gene CASQ2 was markedly up-regulated (~ 2.2-fold) in patients with the orbital disease and/or healthy people by microarray analysis. Zhu and Yang [7] indicated that POMC, IL-2, GNG3, CXCR4, TLR4, CSF1R, LPAR3 and CXCL8 were hub genes among many DEGs. It was also found that 71 DEGs were associated with TED in the comparative Toxicogenomics Database.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to data limitation, the methods used for identifying genes with biological relevance in TED are also limited to differential expression analysis-based approaches. Although studies reported by Rosenbaum et al [6], Zhu and Yang [7] and Lee et al [8] identified some genes related to TED, the unicity of their approach may not help capture some highly TED-related genes. Thus, integrating multiple approaches may help identify the credible key genes associated with TED.…”

Section: Introductionmentioning

confidence: 96%

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Construction of the coexpression network involved in the pathogenesis of thyroid eye disease via bioinformatics analysis

Zhou

Guo

2022

Hum Genomics

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Background Thyroid eye disease (TED) is the most common orbital pathology that occurs in up to 50% of patients with Graves’ disease. Herein, we aimed at discovering the possible hub genes and pathways involved in TED based on bioinformatical approaches. Results The GSE105149 and GSE58331 datasets were downloaded from the Gene Expression Omnibus (GEO) database and merged for identifying TED-associated modules by weighted gene coexpression network analysis (WGCNA) and local maximal quasi-clique merger (lmQCM) analysis. EdgeR was run to screen differentially expressed genes (DEGs). Transcription factor (TF), microRNA (miR) and drug prediction analyses were performed using ToppGene suite. Function enrichment analysis was used to investigate the biological function of genes. Protein–protein interaction (PPI) analysis was performed based on the intersection between the list of genes obtained by WGCNA, lmQCM and DEGs, and hub genes were identified using the MCODE plugin. Based on the overlap of 497 genes retrieved from the different approaches, a robust TED coexpression network was constructed and 11 genes (ATP6V1A, PTGES3, PSMD12, PSMA4, METAP2, DNAJA1, PSMA1, UBQLN1, CCT2, VBP1 and NAA50) were identified as hub genes. Key TFs regulating genes in the TED-associated coexpression network, including NFRKB, ZNF711, ZNF407 and MORC2, and miRs including hsa-miR-144, hsa-miR-3662, hsa-miR-12136 and hsa-miR-3646, were identified. Genes in the coexpression network were enriched in the biological processes including proteasomal protein catabolic process and proteasome-mediated ubiquitin-dependent protein catabolic process and the pathways of endocytosis and ubiquitin-mediated proteolysis. Drugs perturbing genes in the coexpression network were also predicted and included enzyme inhibitors, chlorodiphenyl and finasteride. Conclusions For the first time, TED-associated coexpression network was constructed and key genes and their functions, as well as TFs, miRs and drugs, were predicted. The results of the present work may be relevant in the treatment and diagnosis of TED and may boost molecular studies regarding TED.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

Construction of the coexpression network involved in the pathogenesis of thyroid eye disease via bioinformatics analysis

Zhou

Guo

2022

Hum Genomics

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“…Penelitian lebih lanjut bahkan berhasil mengidentifikasikan setidaknya 12 gen (tabel 2) yang mengalami perubahan ekspresi (differentially expressed genes, DEG) pada sampel jaringan adiposa orbital, yang juga diperkirakan berkaitan dengan patofisiologi GO. (45,46) Tabel 1. Protein yang mengalami peningkatan ekspresi pada GO…”

Section: Patofisiologiunclassified

Unveiling Modern Strategies for Diagnosing and Treating Grave Orbitopathy

Ujianto,

Sari,

Rakhman

2024

JK-RISK

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Graves' Orbitopathy (GO), also known as thyroid eye disease or thyroid-associated orbitopathy is characterized by inflammation, ocular muscle hypertrophy, adipogenesis, and oedema (due to glycosaminoglycan accumulation). This condition leads to remodeling, tissue expansion, and/or fibrosis within the fibroadipose tissue or extraocular muscles of the orbit. GO manifests as an extrathyroidal aspect of autoimmune thyroid diseases in both Grave's disease (GD) and Hashimoto's thyroiditis. The pathophysiological foundation of GO entails the infiltration of B cells, T cells, and CD34+ fibroblasts in the orbit. B cells generate IGF (insulin-like growth factor), wherein IGF and TRab (Thyroid-Receptor antibodies) stimulate the IGF receptor complex and thyrotropin receptor (respectively) on the surface of CD34+ cells which triggers orbital tissue expansion, orbital protrusion, optic nerve compression, and eyeball displacement, resulting in exophthalmos. GO progress through an active phase (characterized by inflammation with visible manifestations), followed by a plateau phase (stabilization of GO manifestations), and a gradual resolution of distinctive residual signs and symptoms (inactive phase). This entire process spans between 18-24 months in untreated patients, where disease manifestations significantly depend on the phase during which the disease is identified. GO therapy is intended to shorten the active phase and supress its residual eye manifestations during the inactive phase. In general, GO therapy is categorized into general and disease severity-specific approaches. GO therapy often falls short of providing satisfactory results, prompting need of surgery to address lingering clinical manifestations. This review presents the latest insights into the pathogenesis and treatment of GO for better management and outcomes.

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“…Proteomic investigations of ocular tissues from GO patients have identified 13 proteins (listed in Table 1 ) that are significantly overexpressed and that have connections to tissue inflammation, adipose tissue differentiation, lipid metabolism, and tissue remodeling. Furthermore, analysis of differentially expressed genes (DEGs) in orbital adipose tissue samples led to the identification of 12 hub genes (listed in Table 2 ) [ 33 , 34 ].…”

Section: Pathogenesismentioning

confidence: 99%