Clinical and molecular impact of concurrent thyroid autoimmune disease and thyroid cancer: From the bench to bedside

dos Santos Valsecchi, Victor Alexandre; Betoni, Felipe Rodrigues; Ward, Laura Sterian; Cunha, Lucas Leite

doi:10.1007/s11154-023-09846-w

Cited by 5 publications

(1 citation statement)

References 140 publications

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“…Several studies have indicated a potential link between the presence of CLT and an increased risk of developing DTC [6][7][8]. However, they also showed a protective role of CLT in preventing the spread of DTC by limiting tumor growth to the primary site [9], possibly mediated by the cancer microenvironment [10,11] and cellular cytotoxic and humoral immune reactions [6,12].…”

Section: Introductionmentioning

confidence: 99%

Germline polymorphisms of the NOD2 pathway may predict the effectiveness of radioiodine in differentiated thyroid cancer treatment

Borowczyk,

Kaczmarek-Ryś,

Hryhorowicz

et al. 2024

J Endocrinol Invest

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Purpose Differentiated thyroid cancer (DTC) presents a complex clinical challenge, especially in patients with distant metastases and resistance to standard treatments. This study aimed to investigate the influence of specific genes and their germline single nucleotide polymorphisms (SNPs) linked to both inflammatory processes and other neoplasms on the clinical and pathological characteristics of DTC, particularly their potential impact on radioiodine (RAI) treatment efficacy. Methods This retrospective analysis involved a cohort of 646 patients diagnosed with DTC after thyroidectomy. Study covering 1998–2014, updated in 2023, included 567 women and 79 men (median age: 49; range: 7–83). SNP selection targeted functional significance, while mutational status was assessed by pyrosequencing for comprehensive characterization. Patient genetic profiles were assessed for associations with disease characteristics, RAI response, and cancer pathology. Results Significant correlations emerged between certain SNPs and DTC features. Notably, the NOD2 c.802 T > C variant (rs2066842) was identified as a marker distinguishing between papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC). Moreover, the c.802 T allele was associated with an enhanced response to RAI treatment, indicating a more substantial decrease in posttreatment stimulated thyroglobulin (sTg) concentrations. The NFKB1A allele c.126A (rs696) exhibited connections with lower FTC stages and a reduced probability of multifocality. Conclusion This study explored the molecular mechanisms of particular SNPs, highlighting the role of NOD2 in innate immunity and the stress response, and its potential impact on RAI efficacy. This research underscores the clinical promise of SNP analysis and contributes to personalized treatment strategies for DTC, emphasizing the relevance of genetic factors in cancer progression and treatment outcomes.

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Section: Introductionmentioning

confidence: 99%

Germline polymorphisms of the NOD2 pathway may predict the effectiveness of radioiodine in differentiated thyroid cancer treatment

Borowczyk,

Kaczmarek-Ryś,

Hryhorowicz

et al. 2024

J Endocrinol Invest

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Thyroid cytology in pediatric patients: a single-center study from 2015 to 2023—is there a necessity for distinct treatment approaches for patients with and without autoimmune thyroiditis?

Kujdowicz,

Januś,

Radliński

et al. 2024

Virchows Arch

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The management of thyroid nodules is guided by the cytological classification provided by The Bethesda System for Reporting Thyroid Cytology. Notably, the biology of thyroid tumors in pediatric patients differs from that in adults, and there is limited research focused on pediatric cases. This study aimed to assess the effectiveness of the Bethesda system in pediatric patients treated at the largest tertiary pediatric thyroid center in Poland between 2015 and 2023. A retrospective analysis was conducted on 566 patients with thyroid nodules, of whom 555 underwent fine-needle aspiration biopsy (FNAB). A total of 217 patients underwent thyroid surgery. Of these, 206 had previously undergone FNAB with cytological evaluation at our center, while 11 patients underwent thyroid surgery due to a RET mutation or the need for an extended procedure. The initial FNAB results showed distribution across Bethesda categories as follows: 7.6% for category I, 54.6% for category II, 20.9% for category III, 4.1% for category IV, 7.6% for category V, and 5.6% for category VI. Among patients who underwent surgery, the distribution of Bethesda categories I through VI was 2.9%, 25.2%, 29.1%, 8.3%, 19.4%, and 15%, respectively. The risk of malignancy (ROM) from the initial FNAB was estimated at 33.3%, 11.5%, 22.2%, 4.8%, 84.4%, and 96.8% for Bethesda categories I through VI, respectively. In patients with autoimmune thyroiditis (AIT), the ROM was higher than in non-AIT patients for Bethesda categories I through IV, while it was lower in category VI. The sensitivity for detecting non-benign neoplasms across Bethesda categories III through VI was approximately 86% in both AIT and non-AIT patients. However, for papillary thyroid carcinoma, sensitivity in Bethesda categories V and VI was 86% in non-AIT patients but decreased to 61.5% in AIT patients. These findings emphasize the importance of considering surgical intervention in pediatric patients with Bethesda III-VI cytology, particularly in those with AIT.

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Elucidating the role of Pyroptosis in papillary thyroid cancer: prognostic, immunological, and therapeutic perspectives

Li,

Du,

Kou

et al. 2024

Cancer Cell Int

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Background Pyroptosis, an inflammatory form of programmed cell death, has been implicated in the pathogenesis and progression of several cancers. However, the significance of pyroptosis-related genes (PRGs) in papillary thyroid cancer (PTC) remains unclear. Methods Transcriptome and clinical data of PTC patients were obtained from The Cancer Genome Atlas. The expression patterns of PRGs were identified by consensus clustering. A prognostic model for predicting the thyroid cancer-free interval (TCFi) employed five machine learning methods. Enrichment and immune-related analyses were performed to elucidate the role of pyroptosis. The responses to radioactive iodine (RAI), immune checkpoint inhibitors (ICIs), molecular targeted therapy (MTT), and chemotherapy (CTx) were predicted based on pyroptosis-derived features. Additionally, the expression of prognostic PRGs was validated via six external datasets, 16 cell lines, and 20 pairs of clinical samples. Results PTC patients were classified into three PyroClusters, C1 exhibited BRFA-like tumors with the highest invasiveness and the worst prognosis, C2 presented RAS-like tumors, and C3 was characterized by gene fusion. Nine PRGs (CXCL8, GJA1, H2BC8, IFI27, PRDM1, PYCARD, SEZ6L2, SIGLEC15, TRAF6) were filtered out to construct a PyroScore prognostic model. A derived nomogram demonstrated superior predictive performance than four clinical staging systems. A strong correlation between pyroptosis and tumor immune microenvironment (TIME) remodeling was observed in mechanistic analyses. Patients with a high PyroScore exhibited “hot” tumor immunophenotypes and had a poorer prognosis but could benefit more from ICIs and CTx (such as paclitaxel). Patients with a low PyroScore were more sensitive to RAI and MTT (such as pazopanib and sorafenib). Conclusions PyroScore model can effectively predict TCFi in patients with PTC. Dysregulated expression of PRGs is associated with the TIME modeling. Pyroptosis features have potential significance for developing novel therapeutic strategies for PTC patients.

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Clinical and molecular impact of concurrent thyroid autoimmune disease and thyroid cancer: From the bench to bedside

Cited by 5 publications

References 140 publications

Germline polymorphisms of the NOD2 pathway may predict the effectiveness of radioiodine in differentiated thyroid cancer treatment

Germline polymorphisms of the NOD2 pathway may predict the effectiveness of radioiodine in differentiated thyroid cancer treatment

Thyroid cytology in pediatric patients: a single-center study from 2015 to 2023—is there a necessity for distinct treatment approaches for patients with and without autoimmune thyroiditis?

Elucidating the role of Pyroptosis in papillary thyroid cancer: prognostic, immunological, and therapeutic perspectives

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