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image of Exploring Common Hub Genes in Thyroid Cancer and Hashimoto's Thyroiditis: Diagnostic Insights and Therapeutic Potential with Gefitinib

Abstract

Introduction

Thyroid Cancer (TC) is a prevalent endocrine malignancy with an increasing incidence worldwide, often associated with Hashimoto's Thyroiditis (HT), an autoimmune thyroid disorder. This study aimed to identify and validate key hub genes common to TC and HT and explore their diagnostic, prognostic, and therapeutic roles.

Materials and Methods

Gene expression datasets for TC and HT were analyzed using bioinformatics tools to identify hub genes. In SW579 cells, Gefitinib treatment and siRNA-mediated knockdown of ALDH3A1 and DDX52 were performed, followed by RT-qPCR, Western blot, cell proliferation, colony formation, and wound healing assays.

Results

After analyzing TC and HT datasets, we identified four common dysregulated hub genes: ALDH3A1, DDX52, RASA1, and SPATS2. RT-qPCR confirmed their significant upregulation in TC cell lines compared to normal controls ( < 0.001). ROC analysis demonstrated high diagnostic accuracy, with RASA1 and SPATS2 achieving AUC = 1. Gene expression validation using GSCA and HPA datasets corroborated these findings, and promoter hypomethylation analysis revealed regulatory mechanisms underlying their upregulation. Survival analyses associated elevated ALDH3A1 expression with poor overall survival. Functional assays in TC cells highlighted their oncogenic roles, with knockdown experiments showing reduced proliferation, migration, and colony formation. Immune correlation analyses revealed interactions with immune inhibitors and infiltrates, while miRNA profiling identified tumor-suppressive miRNAs targeting these genes. Drug prediction and molecular docking identified Gefitinib as a promising therapeutic, which effectively suppressed ALDH3A1 and DDX52 expression and oncogenic phenotypes in TC cells.

Conclusion

This study offers comprehensive insights into the molecular underpinnings of TC progression, highlighting the diagnostic and therapeutic potential of these hub genes and their associated regulatory networks. These findings lay a foundation for developing novel therapeutic strategies targeting these genes in TC management.

© 2025 Bentham Science Publishers
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2025-08-29
2025-11-16

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/content/journals/cg/10.2174/0113892029376349250819071649
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Exploring Common Hub Genes in Thyroid Cancer and Hashimoto's Thyroiditis: Diagnostic Insights and Therapeutic Potential with Gefitinib
Bentham Science Publishers ; https://doi.org/10.2174/0113892029376349250819071649
/content/journals/cg/10.2174/0113892029376349250819071649
/content/journals/cg/10.2174/0113892029376349250819071649
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  • Article Type:     Review Article
Keywords: DEGs ; diagnosis ; hashimoto's thyroiditis ; hub genes ; Thyroid cancer

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