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Thyroid Autoimmune Disorders and Cancer
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Thyroid Autoimmune Disorders and Cancer

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 10393

Special Issue Editor

Prof. Dr. Alessandro Antonelli

E-Mail Website
Guest Editor
Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, 56126 Pisa, Italy
Interests: thyroid cancer; autoimmune thyroid diseases; thyroid irAE; Graves’ disease; thyroid eye disease; molecular basis of thyroid cancer; advanced thyroid cancer; tyrosine kinase inhibitors; medullary thyroid cancer; in vitro cell culture
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Immunity and cancer have a functional relationship, and autoimmune phenomena and cancer development are often concomitant. However, scientific literature suggests a multifaceted relationship.

Cancer onset can be associated to the immune stimulus linked to the autoimmune disease, even if the exact mechanisms are still not clear. In fact, a growing incidence of thyroid cancer (TC) and autoimmune thyroid disorders (AITD) has been registered in the last decades, suggesting an association between these pathologies. Elevated thyroid-stimulating hormone (TSH) levels and thyroid autoimmunity are considered as independent risk factors for TC, even if also systemic autoimmunity and inflammation, per se, are risk factors for TC.

However, other studies suggest that the link between inflammation and TC involves multiple components of the immune system, favoring protection against cancer progression. Within the tumor microenvironment, inflammatory cells are connected with endothelial cells, fibroblasts, adipocytes, and extracellular matrix through cytokines, chemokines and adipocytokines.

In this Issue, we aim to shed new light on the intricate connections between thyroid autoimmunity and cancer.

Prof. Dr. Alessandro Antonelli
Guest Editor

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Keywords

  • thyroid autoimmunity
  • thyroid cancer
  • autoimmune thyroid disorders

Published Papers (5 papers)

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Research

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12 pages, 1172 KiB  
Article
Role of Inflammatory Biomarkers (NLR, LMR, PLR) in the Prognostication of Malignancy in Indeterminate Thyroid Nodules
by Claudio Gambardella, Federico Maria Mongardini, Maddalena Paolicelli, Davide Bentivoglio, Giovanni Cozzolino, Roberto Ruggiero, Alessandra Pizza, Salvatore Tolone, Gianmattia del Genio, Simona Parisi, Luigi Brusciano, Loredana Cerbara, Ludovico Docimo and Francesco Saverio Lucido
Int. J. Mol. Sci. 2023, 24(7), 6466; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24076466 - 30 Mar 2023
Cited by 4 | Viewed by 1581
Abstract
Indeterminate follicular thyroid lesions (Thyr 3A and 3B) account for 10% to 30% of all cytopathologic diagnoses, and their unpredictable behavior represents a hard clinical challenge. The possibility to preoperatively predict malignancy is largely advocated to establish a tailored surgery, preventing diagnostic thyroidectomy. [...] Read more.
Indeterminate follicular thyroid lesions (Thyr 3A and 3B) account for 10% to 30% of all cytopathologic diagnoses, and their unpredictable behavior represents a hard clinical challenge. The possibility to preoperatively predict malignancy is largely advocated to establish a tailored surgery, preventing diagnostic thyroidectomy. We analyzed the role of the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR) and the lymphocyte-to-monocyte ratio (LMR) as prognostic factors of malignancy for indeterminate thyroid nodules. In patients affected by cytological Thyr 3A/3B nodules, NLR, PLR and LMR were retrospectively compared and correlated with definitive pathology malignancy, utilizing student’s t-test, ROC analysis and logistic regression. One-hundred and thirty-eight patients presented a Thyr 3A and 215 patients presented a Thyr 3B. After the logistic regression, in Thyr 3A, none of the variables were able to predict malignancy. In Thyr 3B, NLR prognosticated thyroid cancer with an AUC value of 0.685 (p < 0.0001) and a cut-off of 2.202. The NLR results were also similar when considering the overall cohort. The use of cytological risk stratification in addressing the management of indeterminate thyroid nodules in patients is not always reliable. NLR is an easy and reproducible inflammatory biomarker capable of improving the accuracy of preoperative prognostication of malignancy. Full article
(This article belongs to the Special Issue Thyroid Autoimmune Disorders and Cancer)
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17 pages, 2074 KiB  
Article
Bioinformatics and Connectivity Map Analysis Suggest Viral Infection as a Critical Causative Factor of Hashimoto’s Thyroiditis
by Dong-Woo Lim, Min-Seo Choi and Seok-Mo Kim
Int. J. Mol. Sci. 2023, 24(2), 1157; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24021157 - 06 Jan 2023
Cited by 4 | Viewed by 2193
Abstract
Hashimoto’s thyroiditis (HT) is a common autoimmune disease, and its prevalence is rapidly increasing. Both genetic and environmental risk factors contribute to the development of HT. Recently, viral infection has been suggested to act as a trigger of HT by eliciting the host [...] Read more.
Hashimoto’s thyroiditis (HT) is a common autoimmune disease, and its prevalence is rapidly increasing. Both genetic and environmental risk factors contribute to the development of HT. Recently, viral infection has been suggested to act as a trigger of HT by eliciting the host immune response and subsequent autoreactivity. We analyzed the features of HT through bioinformatics analysis so as to identify the markers of HT development. We accessed public microarray data of HT patients from the Gene Expression Omnibus (GEO) and obtained differentially expressed genes (DEGs) under HT. Gene Ontology (GO) and KEGG-pathway-enrichment analyses were performed for functional clustering of our protein–protein interaction (PPI) network. Utilizing ranked gene lists, we performed a Gene Set Enrichment Analysis (GSEA) by using the clusterprofiler R package. By comparing the expression signatures of the huge perturbation database with the queried rank-ordered gene list, a connectivity map (CMap) analysis was performed to screen potential therapeutic targets and agents. The gene expression profile of the HT group was in line with the general characteristics of HT. Biological processes related to the immune response and viral infection pathways were obtained for the upregulated DEGs. The GSEA results revealed activation of autoimmune-disease-related pathways and several viral-infection pathways. Autoimmune-disease and viral-infection pathways were highly interconnected by common genes, while the HLA genes, which are shared by both, were significantly upregulated. The CMap analysis suggested that perturbagens, including SRRM1, NLK, and CCDC92, have the potential to reverse the HT expression profile. Several lines of evidence suggested that viral infection and the host immune response are activated during HT. Viral infection is suspected to act as a key trigger of HT by causing autoimmunity. SRRM1, an alternative splicing factor which responds to viral activity, might serve as potential marker of HT. Full article
(This article belongs to the Special Issue Thyroid Autoimmune Disorders and Cancer)
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13 pages, 2365 KiB  
Article
Sinomenine Hydrochloride Promotes TSHR-Dependent Redifferentiation in Papillary Thyroid Cancer
by Jing Zhang, Aomei Zhao, Xi Jia, Xinru Li, Yiqian Liang, Yan Liu, Xin Xie, Xijie Qu, Qi Wang, Yuemin Zhang, Rui Gao, Yan Yu and Aimin Yang
Int. J. Mol. Sci. 2022, 23(18), 10709; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231810709 - 14 Sep 2022
Cited by 5 | Viewed by 1710
Abstract
Radioactive iodine (RAI) plays an important role in the diagnosis and treatment of papillary thyroid cancer (PTC). The curative effects of RAI therapy are not only related to radiosensitivity but also closely related to the accumulation of radionuclides in the lesion in PTC. [...] Read more.
Radioactive iodine (RAI) plays an important role in the diagnosis and treatment of papillary thyroid cancer (PTC). The curative effects of RAI therapy are not only related to radiosensitivity but also closely related to the accumulation of radionuclides in the lesion in PTC. Sinomenine hydrochloride (SH) can suppress tumor growth and increase radiosensitivity in several tumor cells, including PTC. The aim of this research was to investigate the therapeutic potential of SH on PTC cell redifferentiation. In this study, we treated BCPAP and TPC-1 cells with SH and tested the expression of thyroid differentiation-related genes. RAI uptake caused by SH-pretreatment was also evaluated. The results indicate that 4 mM SH significantly inhibited proliferation and increased the expression of the thyroid iodine-handling gene compared with the control group (p < 0.005), including the sodium/iodide symporter (NIS). Furthermore, SH also upregulated the membrane localization of NIS and RAI uptake. We further verified that upregulation of NIS was associated with the activation of the thyroid-stimulating hormone receptor (TSHR)/cyclic adenosine monophosphate (cAMP) signaling pathway. In conclusion, SH can inhibit proliferation, induce apoptosis, promote redifferentiation, and then increase the efficacy of RAI therapy in PTC cells. Thus, our results suggest that SH could be useful as an adjuvant therapy in combination with RAI therapy in PTC. Full article
(This article belongs to the Special Issue Thyroid Autoimmune Disorders and Cancer)
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Review

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20 pages, 371 KiB  
Review
Combination Strategies Involving Immune Checkpoint Inhibitors and Tyrosine Kinase or BRAF Inhibitors in Aggressive Thyroid Cancer
by Francesca Ragusa, Silvia Martina Ferrari, Giusy Elia, Sabrina Rosaria Paparo, Eugenia Balestri, Chiara Botrini, Armando Patrizio, Valeria Mazzi, Giovanni Guglielmi, Rudy Foddis, Claudio Spinelli, Salvatore Ulisse, Alessandro Antonelli and Poupak Fallahi
Int. J. Mol. Sci. 2022, 23(10), 5731; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23105731 - 20 May 2022
Cited by 8 | Viewed by 2440
Abstract
Thyroid cancer is the most common (~90%) type of endocrine-system tumor, accounting for 70% of the deaths from endocrine cancers. In the last years, the high-throughput genomics has been able to identify pathways/molecular targets involved in survival and tumor progression. Targeted therapy and [...] Read more.
Thyroid cancer is the most common (~90%) type of endocrine-system tumor, accounting for 70% of the deaths from endocrine cancers. In the last years, the high-throughput genomics has been able to identify pathways/molecular targets involved in survival and tumor progression. Targeted therapy and immunotherapy individually have many limitations. Regarding the first one, although it greatly reduces the size of the cancer, clinical responses are generally transient and often lead to cancer relapse after initial treatment. For the second one, although it induces longer-lasting responses in cancer patients than targeted therapy, its response rate is lower. The individual limitations of these two different types of therapies can be overcome by combining them. Here, we discuss MAPK pathway inhibitors, i.e., BRAF and MEK inhibitors, combined with checkpoint inhibitors targeting PD-1, PD-L1, and CTLA-4. Several mutations make tumors resistant to treatments. Therefore, more studies are needed to investigate the patient’s individual tumor mutation burden in order to overcome the problem of resistance to therapy and to develop new combination therapies. Full article
(This article belongs to the Special Issue Thyroid Autoimmune Disorders and Cancer)

Other

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7 pages, 714 KiB  
Case Report
Two Cases of Autoimmune Thyroid Disorders after COVID Vaccination in Dialysis Patients
by Georgios Lioulios, Ioannis Tsouchnikas, Chrysostomos Dimitriadis, Panagiotis Giamalis, Eva Pella, Michalis Christodoulou, Maria Stangou and Aikaterini Papagianni
Int. J. Mol. Sci. 2022, 23(19), 11492; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231911492 - 29 Sep 2022
Cited by 3 | Viewed by 1779
Abstract
SARS-CoV-2 infection and vaccination have been associated with autoimmune thyroid dysfunctions. Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) and molecular mimicry have been referred to as potential causes. Such a case has not been reported in immunocompromised end-stage renal disease (ESRD) patients. Herein we [...] Read more.
SARS-CoV-2 infection and vaccination have been associated with autoimmune thyroid dysfunctions. Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) and molecular mimicry have been referred to as potential causes. Such a case has not been reported in immunocompromised end-stage renal disease (ESRD) patients. Herein we present two dialysis patients with no previous history of thyroid disease who developed immune mediated thyroid disorders after BNT162b mRNA vaccine against SARS-CoV-2. The first patient is a 29-year-old man on hemodialysis diagnosed with Grave’s disease four months post-vaccination and the second one is a 67-year-old female on peritoneal dialysis who developed Hashimoto’s thyroiditis two months post-vaccination. Grave’s disease is uncommon in dialysis patients, whereas Hashimoto’s thyroiditis has a higher incidence in this population. Time proximity in both cases suggests potential causality. To our knowledge, this is the first report of de novo immune-mediated thyroid disorders in dialysis patients following vaccination against SARS-CoV-2. Full article
(This article belongs to the Special Issue Thyroid Autoimmune Disorders and Cancer)
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