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Biomedicines
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Thyroid Cancer: From Biology to Therapeutic Opportunities
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Thyroid Cancer: From Biology to Therapeutic Opportunities

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 10720

Special Issue Editors

Dr. Cristina Alina Silaghi

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Guest Editor
Department of Endocrinology, “Iuliu Hațieganu” University of Medicine and Pharmacy Cluj-Napoca, 8 Victor Babes Street, 400012 Cluj-Napoca, Romania
Interests: thyroid cancer; pituitary tumors; GH deficiency
Prof. Dr. Carmen Emanuela Georgescu

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Guest Editor
Department of Endocrinology, "Iuliu Hatieganu" University of Medicine and Pharmacy Cluj-Napoca, 8 Victor Babes Street, 400012 Cluj-Napoca, Romania
Interests: thyroid cancer; (neuro)endocrine tumors; polycystic ovary syndrome; pituitary tumors; GH deficiency
Dr. Horaţiu Silaghi

E-Mail Website
Guest Editor
Department of Surgery V, "Iuliu Hatieganu" University of Medicine and Pharmacy Cluj-Napoca, 8 Victor Babes Street, 400012 Cluj-Napoca, Romania
Interests: thyroid surgery; endocrine tumors; endocrine surgery

Special Issue Information

Dear Colleagues,

Thyroid cancer (TC) is the most common endocrine neoplasia, accounting for 3.4% of all cancers diagnosed annually. The incidence of TC has increased significantly over the past three decades. TC is predicted to be the second most diagnosed cancer in women and ninth in men by 2030 in the United States. In recent years, TC studies have dramatically improved the understanding of the molecular mechanisms leading to the initiation and progression of TC.

Next-generation sequencing techniques have facilitated the detection of genomic alterations, furthermore, the discovery of molecular pathways, as well as metabolic and immunologic implications related to TC development. Many of these molecular mechanisms have been the basis for the most recent drug development and have stimulated new investigations for future therapeutic strategies. The fight against TC is now in a new era of targeted molecular therapies. Tyrosine kinase inhibitors have become a new therapeutic option for differentiated and medullary TC. Furthermore, the promising results of the immune checkpoint inhibitors used in patients with TC highlight the critical role of the immune system in TC advancement. Furthermore, the recent achievements in molecular biology represent the starting point for new genetic and epigenetic research aiming to delve into thyroid carcinogenesis and, consequently, help to achieve a better outcome in advanced TC cases.

This Special Issue aims to present the latest research in the molecular landscape, which may contribute to decoding pathogenesis, refining diagnosis, prognosis, and therapy of TC. You are welcome to submit for publication systematic or narrative reviews, original research, animal or cell culture models that provide new insights into the molecular mechanisms and may have an impact on TC management.

We look forward to receiving your contributions.

Dr. Cristina Alina Silaghi
Prof. Dr. Carmen Emanuela Georgescu
Dr. Horaţiu Silaghi
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • differentiated thyroid cancer
  • medullary thyroid cancer
  • anaplastic thyroid carcinoma
  • advanced/metastatic thyroid cancer
  • refractory thyroid cancer
  • molecular biomarkers
  • oncogenic signalling pathways
  • imagistic diagnosis
  • thyroid cytology
  • targeted therapy
  • tyrosine kinase inhibitors
  • immune checkpoint inhibitors
  • therapeutic strategies
  • thyroid cancer prognosis
  • epigenomics in thyroid cancer

Published Papers (6 papers)

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Research

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17 pages, 2609 KiB  
Article
MicroRNA Expression Profiling—Potential Molecular Discrimination of Papillary Thyroid Carcinoma Subtypes
by Horatiu Silaghi, Laura Ancuța Pop, Carmen Emanuela Georgescu, Diana Muntean, Doinița Crișan, Patricia Silaghi, Ionela Lungu, Bogdana Adriana Nasui, Eva-H. Dulf, Cornelia Braicu, Ioana Berindan-Neagoe and Cristina Alina Silaghi
Biomedicines 2024, 12(1), 136; https://doi.org/10.3390/biomedicines12010136 - 09 Jan 2024
Viewed by 679
Abstract
Recent research has revealed the importance of miRNAs in the diagnosis and clinical evolution of papillary thyroid cancer (PTC). We aim to identify a specific miRNA profile that could differentiate between specific subtypes of PTC. Methods: In this cross-sectional study, total RNA was [...] Read more.
Recent research has revealed the importance of miRNAs in the diagnosis and clinical evolution of papillary thyroid cancer (PTC). We aim to identify a specific miRNA profile that could differentiate between specific subtypes of PTC. Methods: In this cross-sectional study, total RNA was extracted from paraffin-embedded tissues of 43 patients, 17 with an infiltrative follicular variant of PTC (iFVPTC) and 26 with a conventional variant of PTC (cPTC). Nine miRNAs were evaluated using qRT-PCR technology and specific miRNA assays. Results: We found specific patterns for cPTC and iFVPTC, such as miRNA altered in both types of tumours (miR-146b-5p, miR-181a-5p, miR-221-3p, miR-21-5p and miR-222-3p) and two miRNAs significantly expressed only in cPTC (miR-20b-5p, miR-21-5p). The iFVPTC group presented strong and moderate correlations between miRNA expression and clinical data. miR-221-3p, miR-195-5p, miR-181-5p, miR-146b-5p and miR-222 were correlated with age, tumour size (TS) or lymph node metastases (N), while only miR-20b-5p, miR-195-5p and miR-181-5p were correlated with TS, N and age in the cPTC group. Conclusions: The present study allowed the identification of a signature of two miRNAs to confirm miRNA differences between the two histological subtypes of TC. Our results provide advances in the molecular diagnosis of TC and could help to improve the diagnostic performance of already existing molecular classifiers. Full article
(This article belongs to the Special Issue Thyroid Cancer: From Biology to Therapeutic Opportunities)
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16 pages, 2974 KiB  
Article
Developing Models to Predict BRAFV600E and RAS Mutational Status in Papillary Thyroid Carcinoma Using Clinicopathological Features and pERK1/2 Immunohistochemistry Expression
by Agnes Stephanie Harahap, Imam Subekti, Sonar Soni Panigoro, Asmarinah, Lisnawati, Retno Asti Werdhani, Hasrayati Agustina, Dina Khoirunnisa, Mutiah Mutmainnah, Fajar Lamhot Gultom, Abdillah Hasbi Assadyk and Maria Francisca Ham
Biomedicines 2023, 11(10), 2803; https://doi.org/10.3390/biomedicines11102803 - 16 Oct 2023
Viewed by 1293
Abstract
The Cancer Genome Atlas (TCGA) has classified papillary thyroid carcinoma (PTC) into indolent RAS-like and aggressive BRAF-like based on its distinct driver gene mutations. This retrospective study aimed to assess clinicopathology and pERK1/2 expression variations between BRAF-like and RAS-like PTCs and establish predictive [...] Read more.
The Cancer Genome Atlas (TCGA) has classified papillary thyroid carcinoma (PTC) into indolent RAS-like and aggressive BRAF-like based on its distinct driver gene mutations. This retrospective study aimed to assess clinicopathology and pERK1/2 expression variations between BRAF-like and RAS-like PTCs and establish predictive models for BRAFV600E and RAS-mutated PTCs. A total of 222 PTCs underwent immunohistochemistry staining to assess pERK1/2 expression and Sanger sequencing to analyze the BRAF and RAS genes. Multivariate logistic regression was employed to develop prediction models. Independent predictors of the BRAFV600E mutation include a nuclear score of 3, the absence of capsules, an aggressive histology subtype, and pERK1/2 levels exceeding 10% (X2 = 0.128, p > 0.05, AUC = 0.734, p < 0.001). The RAS mutation predictive model includes follicular histology subtype and pERK1/2 expression > 10% (X2 = 0.174, p > 0.05, AUC = 0.8, p < 0.001). We propose using the prediction model concurrently with four potential combination group outcomes. PTC cases included in a combination of the low-BRAFV600E-scoring group and high-RAS-scoring group are categorized as RAS-like (adjOR = 4.857, p = 0.01, 95% CI = 1.470–16.049). PTCs included in a combination of the high-BRAFV600E-scoring group and low-RAS-scoring group are categorized as BRAF-like PTCs (adjOR = 3.091, p = 0.001, 95% CI = 1.594–5.995). The different prediction models indicate variations in biological behavior between BRAF-like and RAS-like PTCs. Full article
(This article belongs to the Special Issue Thyroid Cancer: From Biology to Therapeutic Opportunities)
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Review

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17 pages, 559 KiB  
Review
Cancer Predisposition Syndromes and Thyroid Cancer: Keys for a Short Two-Way Street
by Ioana Balinisteanu, Monica-Cristina Panzaru, Lavinia Caba, Maria-Christina Ungureanu, Andreea Florea, Ana Maria Grigore and Eusebiu Vlad Gorduza
Biomedicines 2023, 11(8), 2143; https://doi.org/10.3390/biomedicines11082143 - 29 Jul 2023
Cited by 1 | Viewed by 1198
Abstract
Cancer predisposition syndromes are entities determined especially by germinal pathogenic variants, with most of them autosomal dominantly inherited. The risk of a form of cancer is variable throughout life and affects various organs, including the thyroid. Knowing the heterogeneous clinical picture and the [...] Read more.
Cancer predisposition syndromes are entities determined especially by germinal pathogenic variants, with most of them autosomal dominantly inherited. The risk of a form of cancer is variable throughout life and affects various organs, including the thyroid. Knowing the heterogeneous clinical picture and the existing genotype–phenotype correlations in some forms of thyroid cancer associated with these syndromes is important for adequate and early management of patients and families. This review synthesizes the current knowledge on genes and proteins involved in cancer predisposition syndromes with thyroid cancer and the phenomena of heterogeneity (locus, allelic, mutational, and clinical). Full article
(This article belongs to the Special Issue Thyroid Cancer: From Biology to Therapeutic Opportunities)
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28 pages, 2012 KiB  
Review
Multi-Omics and Management of Follicular Carcinoma of the Thyroid
by Thifhelimbilu Emmanuel Luvhengo, Ifongo Bombil, Arian Mokhtari, Maeyane Stephens Moeng, Demetra Demetriou, Claire Sanders and Zodwa Dlamini
Biomedicines 2023, 11(4), 1217; https://doi.org/10.3390/biomedicines11041217 - 19 Apr 2023
Cited by 3 | Viewed by 3653
Abstract
Follicular thyroid carcinoma (FTC) is the second most common cancer of the thyroid gland, accounting for up to 20% of all primary malignant tumors in iodine-replete areas. The diagnostic work-up, staging, risk stratification, management, and follow-up strategies in patients who have FTC are [...] Read more.
Follicular thyroid carcinoma (FTC) is the second most common cancer of the thyroid gland, accounting for up to 20% of all primary malignant tumors in iodine-replete areas. The diagnostic work-up, staging, risk stratification, management, and follow-up strategies in patients who have FTC are modeled after those of papillary thyroid carcinoma (PTC), even though FTC is more aggressive. FTC has a greater propensity for haematogenous metastasis than PTC. Furthermore, FTC is a phenotypically and genotypically heterogeneous disease. The diagnosis and identification of markers of an aggressive FTC depend on the expertise and thoroughness of pathologists during histopathological analysis. An untreated or metastatic FTC is likely to de-differentiate and become poorly differentiated or undifferentiated and resistant to standard treatment. While thyroid lobectomy is adequate for the treatment of selected patients who have low-risk FTC, it is not advisable for patients whose tumor is larger than 4 cm in diameter or has extensive extra-thyroidal extension. Lobectomy is also not adequate for tumors that have aggressive mutations. Although the prognosis for over 80% of PTC and FTC is good, nearly 20% of the tumors behave aggressively. The introduction of radiomics, pathomics, genomics, transcriptomics, metabolomics, and liquid biopsy have led to improvements in the understanding of tumorigenesis, progression, treatment response, and prognostication of thyroid cancer. The article reviews the challenges that are encountered during the diagnostic work-up, staging, risk stratification, management, and follow-up of patients who have FTC. How the application of multi-omics can strengthen decision-making during the management of follicular carcinoma is also discussed. Full article
(This article belongs to the Special Issue Thyroid Cancer: From Biology to Therapeutic Opportunities)
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17 pages, 713 KiB  
Review
The Role of Genetic Polymorphisms in Differentiated Thyroid Cancer: A 2023 Update
by Robert Aurelian Tiucă, Oana Mirela Tiucă and Ionela Maria Pașcanu
Biomedicines 2023, 11(4), 1075; https://doi.org/10.3390/biomedicines11041075 - 02 Apr 2023
Cited by 1 | Viewed by 2433
Abstract
Thyroid cancer is the most common endocrine malignancy, with an increasing trend in the past decades. It has a variety of different histological subtypes, the most frequent one being differentiated thyroid cancer, which refers to papillary carcinoma, the most common histological type, followed [...] Read more.
Thyroid cancer is the most common endocrine malignancy, with an increasing trend in the past decades. It has a variety of different histological subtypes, the most frequent one being differentiated thyroid cancer, which refers to papillary carcinoma, the most common histological type, followed by follicular carcinoma. Associations between genetic polymorphisms and thyroid cancer have been investigated over the years and are an intriguing topic for the scientific world. To date, the results of associations of single nucleotide polymorphisms, the most common genetic variations in the genome, with thyroid cancer have been inconsistent, but many promising results could potentially influence future research toward developing new targeted therapies and new prognostic biomarkers, thus consolidating a more personalized management for these patients. This review focuses on emphasizing the existing literature data regarding genetic polymorphisms investigated for their potential association with differentiated thyroid cancer and highlights the opportunity of using genetic variations as biomarkers of diagnosis and prognosis for thyroid cancer patients. Full article
(This article belongs to the Special Issue Thyroid Cancer: From Biology to Therapeutic Opportunities)
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Other

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10 pages, 23187 KiB  
Case Report
Aggressive Primary Thyroid Mucoepidermoid Carcinoma with Extensive Pulmonary Involvement
by Marius Mitrache, Dana Terzea, Anca Sirbu and Simona Fica
Biomedicines 2024, 12(2), 285; https://doi.org/10.3390/biomedicines12020285 - 26 Jan 2024
Viewed by 705
Abstract
Mucoepidermoid carcinomas (MECs) represent the most common malignant neoplasms of the salivary glands, but they have also been described in other unusual sites. Primary MECs originating in the thyroid gland are exceedingly rare, accounting for less than 0.5% of thyroid tumors. Owing to [...] Read more.
Mucoepidermoid carcinomas (MECs) represent the most common malignant neoplasms of the salivary glands, but they have also been described in other unusual sites. Primary MECs originating in the thyroid gland are exceedingly rare, accounting for less than 0.5% of thyroid tumors. Owing to their low to medium grade, they are usually associated with an indolent evolution and a good long-term prognosis, generally being managed surgically based on the extent of the disease. However, this does not always apply, as primary thyroid MECs may present as metastatic or locally advanced diseases. While several treatment options have been explored in such cases, no consensus currently exists on their optimal treatment plan, and they should be managed in a multidisciplinary fashion. We report the case of a 67-year-old patient with primary MEC of the thyroid, which behaved aggressively, with extensive pulmonary metastasis, ultimately leading to the rapid clinical deterioration and death of the patient. Full article
(This article belongs to the Special Issue Thyroid Cancer: From Biology to Therapeutic Opportunities)
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