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The Current Understanding of the Molecular Pathogenesis of Papillary Thyroid Cancer
 
 
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Volume 26
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10.3390/ijms26178290
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Papillary Thyroid Carcinoma and Body Mass Index: The Role of Immune System in Tumor Microenvironment

by
Rebecca Sparavelli
1,
Riccardo Giannini
1,
Francesca Signorini
1,
Gabriele Materazzi
2,
Alessio Basolo
3,
Ferruccio Santini
3 and
Clara Ugolini
1,*
1
Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, 56100 Pisa, Italy
2
Endocrine Surgery Unit, Department of Surgical, Medical and Molecular Pathology and Critical Area, Pisa University Hospital, 56126 Pisa, Italy
3
Obesity and Lipodystrophy Center, Endocrinology Unit, Pisa University Hospital, 56124 Pisa, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2025, 26(17), 8290; https://doi.org/10.3390/ijms26178290 (registering DOI)
Submission received: 26 June 2025 / Revised: 8 August 2025 / Accepted: 14 August 2025 / Published: 26 August 2025
(This article belongs to the Special Issue Molecular Biology of the Thyroid Cancer and Thyroid Dysfunctions)
Versions Notes

Abstract

Papillary thyroid cancer (PTC) is linked to obesity, but the biological mechanisms that may explain this connection have been only partially described. Potential factors that combine overweight/obesity with this cancer should be searched for in the immune pathways and chronic inflammation onset. In this study, we evaluated the role of the immune system in patients affected by PTC and stratified them according to Body Mass Index (BMI). An analysis of the expression profiles of >700 immune-related genes was performed in 36 PTCs, subdivided into four categories: underweight (A), normal weight (B), overweight (C), and subjects living with obesity (D). B was considered a reference category. In our study, the immune microenvironment of PTCs did not seem strongly influenced by BMI. However, based on the interaction from in silico protein–protein analysis, we found that the dysregulation profiles of groups A or D were similar as concerns pathways involved in T-cell differentiation, macrophage activation, regulation of the cell cycle, and senescence processes. Furthermore, we found significant downregulation of HMGB1 in the A and D categories, with upregulation of ARG2 in the D category. Although further studies are necessary, these genes may provide an opportunity to better understand immunometabolism in thyroid cancer.
Keywords: PTC; TME; immune system; BMI; thyroid carcinoma; gene expression analysis; ARG2; HGMB1 PTC; TME; immune system; BMI; thyroid carcinoma; gene expression analysis; ARG2; HGMB1

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MDPI and ACS Style

Sparavelli, R.; Giannini, R.; Signorini, F.; Materazzi, G.; Basolo, A.; Santini, F.; Ugolini, C. Papillary Thyroid Carcinoma and Body Mass Index: The Role of Immune System in Tumor Microenvironment. Int. J. Mol. Sci. 2025, 26, 8290. https://doi.org/10.3390/ijms26178290

AMA Style

Sparavelli R, Giannini R, Signorini F, Materazzi G, Basolo A, Santini F, Ugolini C. Papillary Thyroid Carcinoma and Body Mass Index: The Role of Immune System in Tumor Microenvironment. International Journal of Molecular Sciences. 2025; 26(17):8290. https://doi.org/10.3390/ijms26178290

Chicago/Turabian Style

Sparavelli, Rebecca, Riccardo Giannini, Francesca Signorini, Gabriele Materazzi, Alessio Basolo, Ferruccio Santini, and Clara Ugolini. 2025. "Papillary Thyroid Carcinoma and Body Mass Index: The Role of Immune System in Tumor Microenvironment" International Journal of Molecular Sciences 26, no. 17: 8290. https://doi.org/10.3390/ijms26178290

APA Style

Sparavelli, R., Giannini, R., Signorini, F., Materazzi, G., Basolo, A., Santini, F., & Ugolini, C. (2025). Papillary Thyroid Carcinoma and Body Mass Index: The Role of Immune System in Tumor Microenvironment. International Journal of Molecular Sciences, 26(17), 8290. https://doi.org/10.3390/ijms26178290

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