Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
7.4
5.2
Journals
Cancers
Special Issues
The Molecular Basis of Thyroid Cancer
share announcement

The Molecular Basis of Thyroid Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: closed (15 August 2023) | Viewed by 10042

Special Issue Editors

Dr. John H. Yim

E-Mail Website
Guest Editor
City of Hope National Med Center, Duarte, CA, USA
Interests: thyroid nodules; thyroid cancer; parathyroid disease; parathyroid cancer; endocrine disorders; breast cancer
Dr. Maria Hahn

E-Mail Website
Guest Editor
City of Hope National Med Center, Duarte, CA, USA
Interests: epigenetics; genomics; cancer biology; molecular and cellular biology of cancer

Special Issue Information

Dear Colleagues,

Thyroid cancer is by far the most common endocrine malignancy and the ninth most common cancer in the world. Due to the high prevalence in women, thyroid cancer is the 5th most common cancer in women in the world. Thyroid cancer incidence has more than tripled over the past four decades and continues to rise. Significant advances in the molecular characterization of thyroid cancer have dramatically improved our understanding of the molecular mechanisms driving thyroid cancer initiation and progression. Today, molecular markers play an important role in the diagnosis and management of the disease. Molecular analysis of needle biopsy, while imperfect, has been introduced for the pre-operative diagnosis of thyroid nodules with indeterminate cytology to prevent overdiagnosis. To provide the appropriate intervention and prevent overtreatment, risk stratification by molecular markers is already being used to guide patient management, from watchful waiting to aggressive surgery with adjuvant treatment. For advanced disease, molecular testing of thyroid tumors may be able to affect treatment decisions of all types (surgical, nuclear medicine, radiation, small molecule inhibitor, immunotherapy, and chemotherapy) by molecular markers associated with treatment response.

We are pleased to invite you to contribute to a Special Issue in Cancers that will focus on The Molecular Basis of Thyroid Cancer. This Special Issue aims to provide our current understanding of and new insight into the molecular basis of thyroid cancer of all types. In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following: insight into the molecular basis of all forms of aggressive and indolent thyroid cancers, including papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), Hürthle cell cancer, medullary thyroid cancer (MTC), poorly differentiated thyroid cancer (PDTC), anaplastic thyroid cancer (ATC), as well as non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Various topics associated with thyroid cancer including the role of environmental factors, hereditary predisposition, and genetic, epigenetic, and histopathologic changes in thyroid cancer initiation, development, and progression, and their potential clinical implications for diagnosis, prognosis, and in predicting therapeutic efficacies and outcomes; early detection of thyroid cancer or recurrence, mechanisms of development of resistance to therapy are welcome.

We look forward to receiving your contributions.

Dr. John H. Yim
Dr. Maria Hahn
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. Cancers is an international peer-reviewed open access semimonthly 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 2900 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

  • BRAFV600E
  • poorly differentiated thyroid cancer
  • non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)
  • anaplastic thyroid cancer
  • oncogenesis
  • targeted therapy
  • molecular testing
  • oncogenic mutations
  • oncogenic signaling pathways
  • epigenomics of thyroid cancer

Published Papers (6 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

21 pages, 4167 KiB  
Article
SPRY4 as a Potential Mediator of the Anti-Tumoral Role of Macrophages in Anaplastic Thyroid Cancer Cells
by Ana Teresa Pinto, Marta Pojo, Ricardo Rodrigues, Diana Pacheco Sousa, Rune Matthiesen, Ana Sofia Carvalho, Hans C. Beck, Carolina Pires, Rodrigo Eduardo, Joana Simões Pereira, Valeriano Leite and Branca Maria Cavaco
Cancers 2023, 15(17), 4387; https://doi.org/10.3390/cancers15174387 - 1 Sep 2023
Cited by 1 | Viewed by 1135
Abstract
Anaplastic thyroid carcinoma (ATC) is the most lethal subtype of thyroid cancer, with high invasive and metastatic potential, not responding to conventional treatments. Its aggressiveness may be influenced by macrophages, which are abundant cells in the tumor microenvironment. To investigate the role of [...] Read more.
Anaplastic thyroid carcinoma (ATC) is the most lethal subtype of thyroid cancer, with high invasive and metastatic potential, not responding to conventional treatments. Its aggressiveness may be influenced by macrophages, which are abundant cells in the tumor microenvironment. To investigate the role of macrophages in ATC aggressiveness, indirect co-cultures were established between ATC cell lines and THP-1-derived macrophages. Macrophages significantly increased both the migration and invasion of T235 cells (p < 0.01; p < 0.01), contrasting with a decrease in C3948 (p < 0.001; p < 0.05), with mild effects in T238 migration (p < 0.01) and C643 invasion (p < 0.05). Flow cytometry showed upregulation of CD80 (pro-inflammatory, anti-tumoral) and downregulation of CD163 (anti-inflammatory, pro-tumoral) in macrophages from co-culture with T235 (p < 0.05) and C3948 (p < 0.05), respectively. Accordingly, we found an upregulation of secreted pro-inflammatory mediators (e.g., GM-CSF, IL-1α; p < 0.05) in C3948–macrophage co-cultures. Proteomic analysis showed the upregulation of SPRY4, an inhibitor of the MAPK pathway, in C3948 cells from co-culture. SPRY4 silencing promoted cancer cell invasion, reverting the reduced invasion of C3948 caused by macrophages. Our findings support that macrophages play a role in ATC cell aggressiveness. SPRY4 is a possible modulator of macrophage–ATC cell communication, with a tumor suppressor role relevant for therapeutic purposes. Full article
(This article belongs to the Special Issue The Molecular Basis of Thyroid Cancer)
►▼ Show Figures

Figure 1

16 pages, 5702 KiB  
Article
PLA2R1 Inhibits Differentiated Thyroid Cancer Proliferation and Migration via the FN1-Mediated ITGB1/FAK Axis
by Hui Zheng, Mengyu Zhang, Dingwei Gao, Xiaoying Zhang, Haidong Cai, Zhijun Cui, Yang Gao and Zhongwei Lv
Cancers 2023, 15(10), 2720; https://doi.org/10.3390/cancers15102720 - 11 May 2023
Cited by 2 | Viewed by 1617
Abstract
PLA2R1 is a novel gene that is aberrantly expressed in a variety of malignancies. However, the role and mechanism of PLA2R1 in thyroid cancer has not been elucidated. We aimed to uncover the underlying mechanism of PLA2R1 in thyroid cancer. We collected 115 [...] Read more.
PLA2R1 is a novel gene that is aberrantly expressed in a variety of malignancies. However, the role and mechanism of PLA2R1 in thyroid cancer has not been elucidated. We aimed to uncover the underlying mechanism of PLA2R1 in thyroid cancer. We collected 115 clinical specimens, including 54 tumor tissues and 61 para-cancerous tissues, who underwent surgical treatment at Shanghai Tenth Hospital. Immunohistochemical staining was used to evaluate PLA2R1 expression in differentiated thyroid cancer (DTC) tissues. The thyroid cancer cell lines 8505c and FTC133 transfected with PLA2R1 overexpression or knockdown plasmids were used for CCK8 assays and a wound healing assay. Next, we conducted coimmunoprecipitation (Co-IP) experiments and western blotting to explore the underlying mechanism of PLA2R1 in regulating the growth of thyroid cancer. We discovered that the expression of PLA2R1 was lower in the tumor tissues than in para-cancerous tissues (χ2 = 37.0, p < 0.01). The overexpression of PLA2R1 significantly suppressed thyroid cancer cell proliferation and migration, and both of these effects were partially attenuated by the knockdown of PLA2R1. Furthermore, the in vivo growth of DTC could be alleviated by the knockdown of PLA2R1. The mechanistic study revealed that PLA2R1 competed with FN1 for binding to ITGB1, inhibiting the FAK axis and epithelial-mesenchymal transition (EMT). We speculate that PLA2R1 might be a promising marker and a novel therapeutic target for thyroid cancer. Full article
(This article belongs to the Special Issue The Molecular Basis of Thyroid Cancer)
►▼ Show Figures

Figure 1

30 pages, 18888 KiB  
Article
Androgen Receptor Activation Induces Senescence in Thyroid Cancer Cells
by Anvita Gupta, Michelle Carnazza, Melanie Jones, Zbigniew Darzynkiewicz, Dorota Halicka, Timmy O’Connell, Hong Zhao, Sina Dadafarin, Edward Shin, Monica D. Schwarcz, Augustine Moscatello, Raj K. Tiwari and Jan Geliebter
Cancers 2023, 15(8), 2198; https://doi.org/10.3390/cancers15082198 - 7 Apr 2023
Cited by 3 | Viewed by 2036
Abstract
Thyroid cancer (TC) is the most common endocrine malignancy, with an approximately three-fold higher incidence in women. TCGA data indicate that androgen receptor (AR) RNA is significantly downregulated in PTC. In this study, AR-expressing 8505C (anaplastic TC) (84E7) and K1 (papillary TC) cells [...] Read more.
Thyroid cancer (TC) is the most common endocrine malignancy, with an approximately three-fold higher incidence in women. TCGA data indicate that androgen receptor (AR) RNA is significantly downregulated in PTC. In this study, AR-expressing 8505C (anaplastic TC) (84E7) and K1 (papillary TC) cells experienced an 80% decrease in proliferation over 6 days of exposure to physiological levels of 5α-dihydrotestosterone (DHT). In 84E7, continuous AR activation resulted in G1 growth arrest, accompanied by a flattened, vacuolized cell morphology, with enlargement of the cell and the nuclear area, which is indicative of senescence; this was substantiated by an increase in senescence-associated β-galactosidase activity, total RNA and protein content, and reactive oxygen species. Additionally, the expression of tumor suppressor proteins p16, p21, and p27 was significantly increased. A non-inflammatory senescence-associated secretory profile was induced, significantly decreasing inflammatory cytokines and chemokines such as IL-6, IL-8, TNF, RANTES, and MCP-1; this is consistent with the lower incidence of thyroid inflammation and cancer in men. Migration increased six-fold, which is consistent with the clinical observation of increased lymph node metastasis in men. Proteolytic invasion potential was not significantly altered, which is consistent with unchanged MMP/TIMP expression. Our studies provide evidence that the induction of senescence is a novel function of AR activation in thyroid cancer cells, and may underlie the protective role of AR activation in the decreased incidence of TC in men. Full article
(This article belongs to the Special Issue The Molecular Basis of Thyroid Cancer)
►▼ Show Figures

Graphical abstract

11 pages, 1194 KiB  
Article
Prognostic Indicators of EIF1AX-Mutated Thyroid Tumor Malignancy and Cancer Aggressiveness
by Saruchi Bandargal, Tanya Chen, Marc Philippe Pusztaszeri, Véronique-Isabelle Forest, Sabrina Daniela da Silva and Richard J. Payne
Cancers 2022, 14(24), 6097; https://doi.org/10.3390/cancers14246097 - 11 Dec 2022
Cited by 3 | Viewed by 1632
Abstract
The risk of malignancy (ROM) of EIF1AX-mutated thyroid nodules has been theorized to be contingent on the position of the mutation within the gene and the presence of co-existing mutations. However, due to EIF1AX’s low mutation frequency, sample sizes currently reported [...] Read more.
The risk of malignancy (ROM) of EIF1AX-mutated thyroid nodules has been theorized to be contingent on the position of the mutation within the gene and the presence of co-existing mutations. However, due to EIF1AX’s low mutation frequency, sample sizes currently reported in the literature are too diminutive to appraise the clinical utility of molecular diagnostic testing. The objective of this study was to elucidate prognostic indicators of EIF1AX-mutated thyroid tumors and cancer aggressiveness by examining a large cohort of cytologically indeterminate thyroid nodules (CITNs) that underwent molecular testing and subsequent surgical resection. This is a multicenter study involving 764 subtotal and total thyroidectomy patients that underwent preoperative molecular testing at two quaternary care hospitals. A five-year retrospective review was performed on the 42 charts of patients that opted for surgery following a positive EIF1AX mutation on ThyroseqV3 results from January 2018 to May 2022. Patient demographics, cytopathology results, molecular testing results, and postoperative histopathology were reviewed. Of the 42 surgically resected nodules that harbored an EIF1AX mutation, 16 (38.1%) were benign, six (14.3%) were non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs) or well-differentiated thyroid neoplasms of uncertain malignant potential (WDT-UMPs), and 20 (47.6%) were malignant. An isolated EIF1AX mutation conferred a ROM of 47.6%, whereas the ROM for nodules with at least one additional molecular alteration was 72.7%. The ROM increased to 100% for nodules with at least one additional molecular alteration and the A113_splice site mutation. Six malignant nodules were aggressive, with five having variegated components of poorly differentiated thyroid carcinoma (PDTC). EIF1AX-mutated thyroid nodules are more susceptible to malignancy in the presence of the A113_splice site mutation and when co-mutated with RAS and/or TP53. This deleterious amalgam is associated with aggressive disease and renders these nodules PDTC. A preoperative molecular test finding of an EIF1AX mutation can be a useful tool for thyroid specialists to optimize clinical management. Full article
(This article belongs to the Special Issue The Molecular Basis of Thyroid Cancer)
►▼ Show Figures

Figure 1

Review

Jump to: Research

27 pages, 2011 KiB  
Review
Molecular Basis and Natural History of Medullary Thyroid Cancer: It is (Almost) All in the RET
by Nicolas Sahakian, Frédéric Castinetti and Pauline Romanet
Cancers 2023, 15(19), 4865; https://doi.org/10.3390/cancers15194865 - 5 Oct 2023
Cited by 2 | Viewed by 1782
Abstract
Medullary thyroid cancer (MTC) is a rare disease, which can be either sporadic (roughly 75% of cases) or genetically determined (multiple endocrine neoplasia type 2, due to REarranged during Transfection RET germline mutations, 25% of cases). Interestingly, RET pathogenic variants (mainly M918T) have [...] Read more.
Medullary thyroid cancer (MTC) is a rare disease, which can be either sporadic (roughly 75% of cases) or genetically determined (multiple endocrine neoplasia type 2, due to REarranged during Transfection RET germline mutations, 25% of cases). Interestingly, RET pathogenic variants (mainly M918T) have also been reported in aggressive forms of sporadic MTC, suggesting the importance of RET signalling pathways in the pathogenesis of MTC. The initial theory of RET codon-related MTC aggressiveness has been recently questioned by studies suggesting that this would only define the age at disease onset rather than the aggressiveness of MTC. Other factors might however impact the natural history of the disease, such as RET polymorphisms, epigenetic factors, environmental factors, MET (mesenchymal–epithelial transition) alterations, or even other genetic alterations such as RAS family (HRAS, KRAS, NRAS) genetic alterations. This review will detail the molecular bases of MTC, focusing on RET pathways, and the potential mechanisms that explain the phenotypic intra- and interfamilial heterogeneity. Full article
(This article belongs to the Special Issue The Molecular Basis of Thyroid Cancer)
►▼ Show Figures

Figure 1

12 pages, 1502 KiB  
Review
From Circulating Tumor Cells to Mirna: New Challenges in the Diagnosis and Prognosis of Medullary Thyroid Cancer
by Claudia Ricci, Antonia Salvemini, Cristina Dalmiglio, Maria Grazia Castagna and Silvia Cantara
Cancers 2023, 15(15), 4009; https://doi.org/10.3390/cancers15154009 - 7 Aug 2023
Cited by 2 | Viewed by 1214
Abstract
Medullary thyroid carcinoma (MTC) is a malignant tumor that arises from parafollicular C cells, which are responsible for producing calcitonin. The majority (75%) of MTC cases are sporadic forms, while the remaining (25%) have a hereditary component. In these hereditary cases, MTC can [...] Read more.
Medullary thyroid carcinoma (MTC) is a malignant tumor that arises from parafollicular C cells, which are responsible for producing calcitonin. The majority (75%) of MTC cases are sporadic forms, while the remaining (25%) have a hereditary component. In these hereditary cases, MTC can occur in conjunction with other endocrine disorders (i.e., pheochromocytoma) or as an isolated condition known as familial medullary thyroid carcinoma. The primary genetic mutation associated with the development of MTC, regardless of its hereditary or sporadic nature, is a point mutation in the RET gene. Evaluation of serum calcitonin levels represents the most reliable and sensitive marker for both the initial diagnosis and the postsurgical monitoring of MTC. Unfortunately, most patients do not achieve normalization of postsurgical serum calcitonin (CT) levels after surgery. Therefore, there is a need to find new biomarkers to be used with serum CT in order to increase test sensitivity and specificity. In this review, we summarize the literature from 2010 to 2023 to review the role of circulating tumor cells, cell-free DNA, and miRNA and their application in diagnosis, outcome of MTC, and response to treatments. Full article
(This article belongs to the Special Issue The Molecular Basis of Thyroid Cancer)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-6
Back to TopTop