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image of Dysregulation of the cAMP Signaling Pathway Mediated by Shared Hub Genes: Diagnostic, Prognostic, and Therapeutic Insights into Thyroid Cancer and Graves' Disease

Abstract

Background

Graves' disease and thyroid cancer share overlapping molecular mechanisms that may reveal potential biomarkers and therapeutic targets. Identifying shared hub genes can provide insights into disease progression and improve diagnostic and therapeutic strategies.

Methodology

Gene expression profiles from Graves' disease (GSE71956) and thyroid cancer (GSE153659) datasets were analyzed to identify differentially expressed genes using the limma package. Common genes were determined by cross-dataset comparison, and hub genes were identified using the degree method. CD44, RHOC, HCN4, and MYH10 were validated by RT-qPCR in thyroid cancer and normal cell lines, and their roles were examined through siRNA-mediated knockdown. Genetic and epigenetic alterations were explored using OncoDB and cBioPortal, while functional enrichment and prognostic analyses were performed through DAVID, GeneMANIA, GSCA, and cSurvival databases

Results

Twenty-three common genes were identified, among which CD44, RHOC, HCN4, and MYH10 were significantly upregulated in thyroid cancer. These genes were associated with cAMP signaling and epithelial-mesenchymal transition pathways. Knockdown of CD44 and RHOC reduced proliferation, colony formation, and migration in SW579 cells.

Discussion

The findings suggest that the overlap between autoimmune and oncogenic pathways may promote tumor development through dysregulated signaling in cell adhesion, migration, and inflammation. The identified genes act as molecular mediators linking immune activation in Graves' disease with oncogenic progression in thyroid cancer.

Conclusion

CD44, RHOC, HCN4, and MYH10 serve as potential diagnostic and therapeutic biomarkers, offering new insights into shared mechanisms underlying thyroid autoimmune and malignant diseases.

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2025-08-06
2025-11-29

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Dysregulation of the cAMP Signaling Pathway Mediated by Shared Hub Genes: Diagnostic, Prognostic, and Therapeutic Insights into Thyroid Cancer and Graves' Disease
Bentham Science Publishers ; https://doi.org/10.2174/0113862073389123250723210633
/content/journals/cchts/10.2174/0113862073389123250723210633
/content/journals/cchts/10.2174/0113862073389123250723210633
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  • Article Type:     Research Article
Keywords: biomarker ; Graves' disease ; diagnosis ; therapeutic target ; c-AMP signaling ; thyroid cancer

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