Exploring Common Hub Genes in Thyroid Cancer and Hashimoto's Thyroiditis: Diagnostic Insights and Therapeutic Potential with Gefitinib
Year: 2025
Type: article
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: < 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.
Source: Current Genomics
Authors: Ruqiong Sun, Bing Li, Fenjuan Xu, Juanfei Zhu
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4413998771