Clinical and Pathological Implications of Concurrent Autoimmune Thyroid Disorders and Papillary Thyroid Cancer

Cooccurrences of chronic lymphocytic thyroiditis (CLT) and thyroid cancer (DTC) have been repeatedly reported. Both CLT and DTC, mainly papillary thyroid carcinoma (PTC), share some epidemiological and molecular features. In fact, thyroid lymphocytic inflammatory reaction has been observed in association with PTC at variable frequency, although the precise relationship between the two diseases is still debated. It also remains a matter of debate whether the association with a CLT or even an autoimmune disorder could influence the prognosis of PTC. A better understanding about clinical implications of autoimmunity in concurrent thyroid cancer could raise new insights of thyroid cancer immunotherapy. In addition, elucidating the molecular mechanisms involved in autoimmune disease and concurrent cancer allowed us to identify new therapeutic strategies against thyroid cancer. The objective of this article was to review recent literature on the association of these disorders and its potential significance.

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Clinical and molecular features of papillary thyroid cancer in adolescents and young adults

Cancer ◽

10.1002/cncr.25369 ◽

2010 ◽

Vol 117 (2) ◽

pp. 259-267 ◽

Cited By ~ 42

Author(s):

Menno R. Vriens ◽

Willieford Moses ◽

Julie Weng ◽

Miao Peng ◽

Ann Griffin ◽

...

Keyword(s):

Young Adults ◽

Thyroid Cancer ◽

Papillary Thyroid Cancer ◽

Adolescents And Young Adults ◽

Papillary Thyroid ◽

Molecular Features

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TREM1 fosters an immunosuppressive tumor microenvironment in papillary thyroid cancer

Endocrine Related Cancer ◽

10.1530/erc-21-0297 ◽

2021 ◽

Author(s):

Yang Zhao ◽

Cangang Zhang ◽

Yanan Zhu ◽

Xi Ding ◽

Yikun Zhou ◽

...

Keyword(s):

T Cells ◽

Thyroid Cancer ◽

Papillary Thyroid Cancer ◽

Molecular Mechanisms ◽

Methylation Status ◽

Disease Free Survival ◽

Papillary Thyroid ◽

Advanced Tumor ◽

Tumor Stages ◽

Immunosuppressive Microenvironment

The immunosuppressive microenvironment is associated with poor prognosis in papillary thyroid cancer (PTC); however, the molecular mechanisms involved are unknown. Among triggering receptor expressed on myeloid cell (TREM) family, we found that TREM1 expression in PTC was significantly higher than that in normal tissues. TREM1 overexpression was associated with BRAFV600E profiles and advanced tumor stages. Furthermore, TREM1 mRNA expression was negatively correlated with promoter methylation status. Specifically, hypomethylation of CpG site cg06196379 in the TREM1 promoter was related with poor patient disease free survival (DFS) and a high PTC recurrence rate. Mechanistically, TREM1 was mainly expressed in malignant epithelial cells but not macrophages in PTC by single-cell analysis. PTC tissues with high TREM1 levels had enhanced infiltration of regulatory T cells (Tregs) and decreased infiltration of CD8+ T cells. Our study confirms that hypomethylation-mediated overexpression of TREM1 in PTC cells promotes an immunosuppressive microenvironment by enhancing Treg infiltration. We recommend the future use of therapeutic strategy targeting TREM1 for the treatment of PTC.

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Acquired Hemophilia A (FVIII Deficiency) Associated with Papillary Thyroid Cancer: Treatment with Recombinant Porcine FVIII

Case Reports in Hematology ◽

10.1155/2019/9026121 ◽

2019 ◽

Vol 2019 ◽

pp. 1-5

Author(s):

S. Nguyen ◽

P. Teh ◽

J. Zhou ◽

E. Y. Chang ◽

A. von Drygalski

Keyword(s):

Thyroid Cancer ◽

Papillary Thyroid Cancer ◽

Hemophilia A ◽

Autoimmune Disorder ◽

Bleeding Complications ◽

Papillary Thyroid ◽

Acquired Hemophilia A ◽

Acquired Hemophilia ◽

Rescue Treatment ◽

Bypassing Agents

Acquired hemophilia A (AHA) is a rare autoimmune disorder caused by autoantibodies against Factor VIII (FVIII). It has a high mortality due to bleeding complications. FVIIa-based bypassing agents are the first line of treatment but not always effective. Recombinant porcine (rp) FVIII (Obizur®) was recently approved for rescue treatment but with little evidence-based information regarding efficacy. We report a case of papillary thyroid cancer associated with AHA malignancy that responded to a single dose of rpFVIII after failure to achieve hemostasis with FVIIa-based bypassing products.

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One-third of an Archivial Series of Papillary Thyroid Cancer (Years 2007–2015) Has Coexistent Chronic Lymphocytic Thyroiditis, Which Is Associated with a More Favorable Tumor-Node-Metastasis Staging

Frontiers in Endocrinology ◽

10.3389/fendo.2017.00337 ◽

2017 ◽

Vol 8 ◽

Cited By ~ 18

Author(s):

Antonio Ieni ◽

Roberto Vita ◽

Emilia Magliolo ◽

Mariacarmela Santarpia ◽

Flavia Di Bari ◽

...

Keyword(s):

Thyroid Cancer ◽

Papillary Thyroid Cancer ◽

Chronic Lymphocytic Thyroiditis ◽

Papillary Thyroid ◽

Tumor Node Metastasis ◽

Lymphocytic Thyroiditis ◽

Node Metastasis ◽

Tumor Node Metastasis Staging

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Comprehensive Analysis of Prognostic Alternative Splicing Signature Reveals Recurrence Predictor for Papillary Thyroid Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.705929 ◽

2021 ◽

Vol 11 ◽

Author(s):

Mian Liu ◽

Rooh Afza Khushbu ◽

Pei Chen ◽

Hui-Yu Hu ◽

Neng Tang ◽

...

Keyword(s):

Thyroid Cancer ◽

Alternative Splicing ◽

Papillary Thyroid Cancer ◽

Molecular Mechanisms ◽

Prediction Models ◽

Cox Regression ◽

Prognostic Biomarkers ◽

Papillary Thyroid ◽

Network Diagram ◽

Prognostic Prediction

BackgroundAlternative splicing (AS) plays a key role in the diversity of proteins and is closely associated with tumorigenicity. The aim of this study was to systemically analyze RNA alternative splicing (AS) and identify its prognostic value for papillary thyroid cancer (PTC).MethodsAS percent-splice-in (PSI) data of 430 patients with PTC were downloaded from the TCGA SpliceSeq database. We successfully identified recurrence-free survival (RFS)-associated AS events through univariate Cox regression, LASSO regression and multivariate regression and then constructed different types of prognostic prediction models. Gene function enrichment analysis revealed the relevant signaling pathways involved in RFS-related AS events. Simultaneously, a regulatory network diagram of AS and splicing factors (SFs) was established.ResultsWe identified 1397 RFS-related AS events which could be used as the potential prognostic biomarkers for PTC. Based on these RFS-related AS events, we constructed a ten-AS event prognostic prediction signature that could distinguish high-and low-risk patients and was highly capable of predicting PTC patient prognosis. ROC curve analysis revealed the excellent predictive ability of the ten-AS events model, with an area under the curve (AUC) value of 0.889; the highest prediction intensity for one-year RFS was 0.923, indicating that the model could be used as a prognostic biomarker for PTC. In addition, the nomogram constructed by the risk score of the ten-AS model also showed high predictive efficiency for the prognosis of PTC patients. Finally, the constructed SF-AS network diagram revealed the regulatory role of SFs in PTC.ConclusionThrough the limited analysis, AS events could be regarded as reliable prognostic biomarkers for PTC. The splicing correlation network also provided new insight into the potential molecular mechanisms of PTC.

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Chronic lymphocytic thyroiditis (CLT) has a negative prognostic value in papillary thyroid cancer of the young and middle ages: a retrospective analysis of 635 patients

10.21203/rs.3.rs-18952/v1 ◽

2020 ◽

Author(s):

Bing'e Ma ◽

Xiyi Chen ◽

Zhengping Zhao ◽

Qin Ji ◽

Yifan Zhou ◽

...

Keyword(s):

Thyroid Cancer ◽

High Risk ◽

Prognostic Value ◽

Age Groups ◽

Recurrence Risk ◽

Lesion Size ◽

Chronic Lymphocytic Thyroiditis ◽

Papillary Thyroid ◽

Lymphocytic Thyroiditis ◽

Risk Recurrence

Abstract Background: The study was aimed at investigating the potential role of chronic lymphocytic thyroiditis (CLT) in papillary thyroid cancer (PTC) prognosis in distinct age groups, as well as the association between CLT and recurrence risk estimation.Methods: A total of 635 adult patients were retrospectively analyzed. On the basis of postoperative pathology examination, 188 patients were diagnosed with coexistent CLT and the remaining 447 were classified as non-CLT. Then the characteristics of CLT-coexisted patients and non-CLT ones were compared respectively when patients were aged ≥55 years or below. The association among postoperative clinicopathological features were also analyzed using multivariate regression. In addition, the prognostic value of several variables relating to high-risk recurrence were estimated within different age groups.Results: When divided in two age groups (55 years as the line), non-CLT group had a remarkable frequency of small size lesion (D max ≤1cm) compared with CLT-coexisted patients (54.6% to 43.0%, p =0.016). In addition, non-CLT patients tended to have intrathyroidal extension as opposed to those with coexistent CLT (20.2% to 28.2%, p =0.05). In multivariate analysis, CLT still significantly acted as an independent risk factor of greater lesion size (D min >1 cm) (OR=1.7, p =0.02) and mildly promoted gross extrathyroidal extension (ETE) (OR=1.4, p =0.06). However, associations didn't emerge in the characteristics mentioned above with CLT when patients were ≥55 years old. The prognostic value of CLT in high-risk recurrence was evident only in patients aged 35-44 years. (OR=2.4, 95%CI:1.2-5.4, p =0.02). Greater lesion size independently promoted gross ETE, no matter patients were aged above 55 years or not. Besides, its prognostic value of high-risk recurrence was significant throughout all age groups. Conclusion: These findings revealed that CLT coexistence might be the unfavorable factor of PTC prognosis in young and middle-aged (<55 years) patients, and its role in recurrence risk stratification was presented only in the specific age (35-44 years).

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Effects of Biological Therapies on Molecular Features of Rheumatoid Arthritis

International Journal of Molecular Sciences ◽

10.3390/ijms21239067 ◽

2020 ◽

Vol 21 (23) ◽

pp. 9067

Author(s):

Chary Lopez-Pedrera ◽

Nuria Barbarroja ◽

Alejandra M. Patiño-Trives ◽

Maria Luque-Tévar ◽

Eduardo Collantes-Estevez ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Molecular Mechanisms ◽

Adaptive Immune System ◽

Autoimmune Disorder ◽

Synovial Fibroblasts ◽

Chronic Inflammatory Disease ◽

Pharmacological Therapy ◽

Biologic Dmards ◽

Molecular Features ◽

Specific Effects

Rheumatoid arthritis (RA) is an autoimmune and chronic inflammatory disease primarily affecting the joints, and closely related to specific autoantibodies that mostly target modified self-epitopes. Relevant findings in the field of RA pathogenesis have been described. In particular, new insights come from studies on synovial fibroblasts and cells belonging to the innate and adaptive immune system, which documented the aberrant production of inflammatory mediators, oxidative stress and NETosis, along with relevant alterations of the genome and on the regulatory epigenetic mechanisms. In recent years, the advances in the understanding of RA pathogenesis by identifying key cells and cytokines allowed the development of new targeted disease-modifying antirheumatic drugs (DMARDs). These drugs considerably improved treatment outcomes for the majority of patients. Moreover, numerous studies demonstrated that the pharmacological therapy with biologic DMARDs (bDMARDs) promotes, in parallel to their clinical efficacy, significant improvement in all these altered molecular mechanisms. Thus, continuous updating of the knowledge of molecular processes associated with the pathogenesis of RA, and on the specific effects of bDMARDs in the correction of their dysregulation, are essential in the early and correct approach to the treatment of this complex autoimmune disorder. The present review details basic mechanisms related to the physiopathology of RA, along with the core mechanisms of response to bDMARDs.

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