Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Papillary Thyroid Carcinoma. Core disease mechanisms, molecular and cellul...

This report is retrieval-only and is generated directly from Asta results.

• Papers retrieved: 19
• Snippets retrieved: 20

Relevant Papers

[1] Insights in biomarkers complexity and routine clinical practice for the diagnosis of thyroid nodules and cancer

• Authors: M. G. de Matos, Mafalda Pinto, A. Gonçalves, Sule Canberk, M. J. Bugalho et al.
• Year: 2025
• Venue: PeerJ
• URL: https://www.semanticscholar.org/paper/655de68f1a7e8137dcba8a2046f14dee4f07594d
• DOI: 10.7717/peerj.18801
• PMID: 39850836
• PMCID: 11756370
• Citations: 4
• Summary: The knowledge of genetic and molecular biomarkers has achieved a high level of complexity, and the difficulties related to its applicability determine that their implementation in clinical practice is not yet a reality.
• Evidence snippets:
• Snippet 1 (score: 0.617) > Knowledge of molecular mechanisms implicated in thyroid carcinogenesis has been attained in recent years. Thyroid neoplasm result from alterations in gene expression patterns, which occur due to a gradual accumulation of genetic and epigenetic events. These changes are associated with specific tumor phenotypes and are implicated in disease etiology. Molecular alterations induce the activation of different signaling pathways, such as the mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3-kinase (PI3K/AKT/mTOR), which are involved in and promote carcinogenesis (Hsiao & Nikiforov, 2014). In a few years, the knowledge of molecular mechanisms implicated in thyroid carcinogenesis changed from understanding signaling pathways and identification of a few genes mutations to the knowledge of the main genes implicated in thyroid carcinogenesis, reviewed by De Leo et al. (2024). Genetic changes in thyroid neoplasms were divided in early/driver molecular alterations and late/progression events. Late/ progression events may be associated with early/driver molecular alterations and represent the evolution from well-differentiated to high-grade and undifferentiated carcinoma, being (Pozdeyev et al., 2018). Most frequent gene mutations present in follicular-cell derived thyroid tumors are BRAF, RAS, and TERTp mutations, associate with clinically relevant clinicopathologic features, as shown in Table 3.

[2] Redox metabolism correlates with cellular turnover and clinical phenotype of papillary thyroid carcinoma and colloid goiter

• Authors: B. Rovčanin, K. Gopčević, D. Kekic, V. Živaljević, A. Diklic et al.
• Year: 2019
• Venue: Archives of Medical Science : AMS
• URL: https://www.semanticscholar.org/paper/acbf6d9a1f376505739b57296f151bed9e8a8373
• DOI: 10.5114/aoms.2019.88374
• PMID: 36160341
• PMCID: 9479590
• Citations: 1
• Summary: PTC tissue is characterized by increased antioxidant activity and a normal prooxidation level, and AOPP is the most powerful predictor of PTC capsular invasion, multicentric intrathyroid dissemination and lymph node metastasis phenotype.
• Evidence snippets:
• Snippet 1 (score: 0.569) > Thyroid neoplasms represent the most common endocrine malignancy, with an increasing incidence over the past decades. Papillary thyroid car-cinoma (PTC) is a well-differentiated thyroid carcinoma, which contributes to approximately 80% of all thyroid malignancies [1]. PTC is frequently multifocal and it usually metastasizes in regional neck lymph nodes while distant metastases are very rare [2]. The clinical course of PTC is benevolent in most patients, as testified by the 90% 5-year survival rate, while the other 10% of patients develop recurrent disease and aggressive clinical progression [3]. Taking into account the frequency of PTC and its clinical importance, it is essential to gain better understanding of its carcinogenesis process. Substantial progress in PTC's molecular pathogenesis has been achieved, on the basis of biochemical, genetic and omics studies. These studies showed the importance of the mitogen-activated protein kinases (MAPK) and phosphatidylinositol 3-kinases-protein kinase B (PI3K-AKT) signaling pathways, whose activation is considered the primary oncogenic event in PTC carcinogenesis, as well as in other pathological states [4,5]. Genetic modifications that account for alterations of these pathways include point mutations, major rearrangements, copy-number variants and changes in gene methylation [6]. In a complex cellular signaling network these two pathways contribute to the regulation of proliferation and apoptosis as well as the redox status, which has a crucial influence on cell survival [7]. Oxidative stress takes place when the large number of generated reactive oxygen species (ROS) cannot be scavenged by cellular antioxidative mechanisms. This state leads to the damage of lipids, proteins and DNA, compromising normal cellular functioning and survival [8]. The extent of oxidative stress is estimated by quantification of biomarkers such as malondialdehyde (MDA) as a marker of lipid peroxidation, advanced oxidation protein products (AOPP) as a marker of oxidative protein damage and 8-oxo-2′-deoxyguanosine (8-oxo-d

[3] Network medicine approaches for identification of novel prognostic systems biomarkers and drug candidates for papillary thyroid carcinoma

• Authors: Medi Kori, Kubra Temiz, E. Gov
• Year: 2023
• Venue: Journal of Cellular and Molecular Medicine
• URL: https://www.semanticscholar.org/paper/94a4aeba681311c594a691c2cd4845397410a4c9
• DOI: 10.1111/jcmm.18002
• PMID: 37859510
• PMCID: 10746936
• Citations: 7
• Summary: The need for differential co‐expression analysis to gain a systems‐level understanding of a complex disease is highlighted, and a candidate prognostic systems biomarker and novel drugs for PTC are provided.
• Evidence snippets:
• Snippet 1 (score: 0.529) > Recent cancer statistics show that thyroid cancer is the most common endocrine cancer encountered by mankind. In 2022, it was estimated that 43,800 patients were diagnosed with thyroid cancer, and thyroid cancer was responsible for 2230 deaths in the United States. 1 Papillary, follicular, medullary, and undifferentiated or anaplastic thyroid carcinomas are the major histologic groups of thyroid tumours. Among the various subgroups of thyroid cancer, papillary thyroid carcinoma (PTC) accounts for the largest proportion of all thyroid carcinomas. Notably, the prevalence of PTC is approximately 85% when all thyroid carcinomas are considered. 2 e aetiology of thyroid cancer is not well understood. Therefore, further studies are needed to uncover the underlying mechanisms of the disease, correct over-diagnosis, and find prognostic and/or drug candidates to reduce the prevalence of PTC. > Logarithmic advances in high-throughput sequencing and screening methods in recent decades have produced a substantial amount of X-ome data at various molecular levels, enabling researchers to perform various bioinformatics approaches for different diseases 3,4 and also for PTC. 5 However, some of these studies take only limited account of the reality of the molecular biochemistry of the organism. To discover specific disease biomarkers or drug targets, it is essential to evaluate the entire physical and functional architecture of the organism, because the development of an abnormal phenotype (i.e. disease) is not the result of a single gene, but rather the result of complex gene interactions. One scientific field, network medicine, allows researchers to uncover these complex interactions between biomolecules of a given phenotype in a holistic view. 6 ne and protein networks provide valuable data for molecular interactions within the organism, and co-expression networks represent significantly co-regulated groups of genes (i.e. modules). Any differentiation in gene correlations between different phenotypes can provide clues to the phenotype and supports the discovery of systems biomarkers. 7 To reveal co-expression relationships among genes in thyroid cancer, weighted gene co-expression network analysis (WGCNA) has been performed in a limited number of studies. 8,9 WGCNA identifies gene modules by hierarchical clustering.

[4] In silico Analysis of Publicly Available Transcriptomics Data Identifies Putative Prognostic and Therapeutic Molecular Targets for Papillary Thyroid Carcinoma

• Authors: A. Almansoori, P. Bhamidimarri, R. Bendardaf, R. Hamoudi
• Year: 2022
• Venue: International Journal of General Medicine
• URL: https://www.semanticscholar.org/paper/6de2046cc1bb187ea53cf5ceef550ba1a4e2b969
• DOI: 10.2147/IJGM.S345336
• PMID: 35330879
• PMCID: 8939872
• Citations: 4
• Summary: Background Thyroid cancer is the most common endocrine malignancy. However, the molecular mechanism involved in its pathogenesis is not well characterized. Purpose The objective of this study is to identify key cellular pathways and differentially expressed genes along the thyroid cancer pathogenesis sequence as well as to identify potential prognostic and therapeutic targets. Methods Publicly available transcriptomics data comprising a total of 95 samples consisting of 41 normal, 28 non-aggr...
• Evidence snippets:
• Snippet 1 (score: 0.517) > Background Thyroid cancer is the most common endocrine malignancy. However, the molecular mechanism involved in its pathogenesis is not well characterized. Purpose The objective of this study is to identify key cellular pathways and differentially expressed genes along the thyroid cancer pathogenesis sequence as well as to identify potential prognostic and therapeutic targets. Methods Publicly available transcriptomics data comprising a total of 95 samples consisting of 41 normal, 28 non-aggressive and 26 metastatic papillary thyroid carcinoma (PTC) cases were used. Transcriptomics data were normalized and filtered identifying 9394 differentially expressed genes. The genes identified were subjected to pathway analysis using absGSEA identifying PTC related pathways. Three of the genes identified were validated on 508 thyroid cancer biopsies using RNAseq and TNMplot. Results Pathway analysis revealed a total of 2193 differential pathways among non-aggressive samples and 1969 among metastatic samples compared to normal tissue. Pathways for non-aggressive PTC include calcium and potassium ion transport, hormone signaling, protein tyrosine phosphatase activity and protein tyrosine kinase activity. Metastatic pathways include growth, apoptosis, activation of MAPK and regulation of serine threonine kinase activity. Genes for non-aggressive are KCNQ1, CACNA1D, KCNN4, BCL2, and PTK2B and metastatic PTC are EGFR, PTK2B, KCNN4 and BCL2. Three of the genes identified were validated using clinical biopsies showing significant overexpression in aggressive compared to non-aggressive PTC; EGFR (p < 0.05), KCNN4 (p < 0.001) and PTK2B (p < 0.001). DrugBank database search identified several FDA approved drug targets including anti-EGFR Vandetanib used to treat thyroid cancer in addition to others that may prove useful in treating PTC. Conclusion Transcriptomics analysis identified putative prognostic targets including EGFR, PTK2B, BCL2, KCNQ1, KCNN4 and CACNA1D. EGFR, PTK2B and KCN44 were validated using thyroid cancer clinical biopsies. The drug search identified FDA approved drugs including
• Snippet 2 (score: 0.509) > Thyroid cancer was ranked as the most common endocrine malignancy. 1 Globally, thyroid cancer incidence has been on the rise over the past three decades. Between 2006 and 2012, the annual incidence rate was 6.5% in women and 5.4 in men. 2,3 In the United States between 2000 and 2009, thyroid cancer incidence rate was the highest among all cancers. 4 The mortality rate of thyroid cancer is considered to be low, whilst the reoccurrence and persistence of the disease is still considered high. 5 Morphologically, thyroid cancers are classified into different cellular subtypes such as papillary, follicular, medullary and anaplastic. Differentiated papillary thyroid carcinoma (PTC) form is the most common type comprising more than 80% of all thyroid cases as shown in Table 1. Genetic mutations have been associated with PTC. 6 Whilst many genomic mutational screening studies were carried out on thyroid cancer in general and PTC in particular, only few have identified mutated genes that are correlated with progression of PTC including TP53 and KRAS/BRAF 7 . However, although such studies suggested that thyroid cancer has high degree of intra-tumoral heterogeneity, 8 the mutations identified did not provide clear insights into the molecular mechanism of thyroid cancer phenotypes and progression. Thus, for better clinical outcomes, there is a compelling need to actively study alterations in cellular pathways linked to the underlying mechanism of thyroid cancer initiation and progression. > Few transcriptomic analyses were carried out on PTC identifying some of the cellular pathways involved in its pathogenesis 9 . However, such studies were generally carried out on small number of patients using standard bioinformatics analysis focusing on list of differentially expressed genes. This provided limited insights into the molecular basis of PTC without clear association to diagnostic, prognostic and therapeutic targets. > In this study, we carried out comprehensive and systematic in silico pathway analysis of PTC using in-house bioinformatics pipeline that has shown good ability to identify the transcriptomic profiles and related differentially expressed genes between different subtypes of the same disease. 10 The aim of this study is to attempt to identify the key transcriptomic signatures that drive non-aggressive and metastatic PTC as well as using such signature to identify putative drug targets

[5] Systems biology approach delineates critical pathways associated with papillary thyroid cancer: a multi-omics data analysis

• Authors: Febby Payva, Santhy K. S., Remya James, Amrisa Pavithra E, Venketesh Sivaramakrishnan
• Year: 2025
• Venue: Thyroid Research
• URL: https://www.semanticscholar.org/paper/73aae1bf968c7f2bd94ee5aae5bbe4dd480c8a86
• DOI: 10.1186/s13044-025-00230-1
• PMID: 40211357
• PMCID: 11987294
• Summary: Papillary thyroid cancer (PTC) is the most prevalent follicular cell-derived subtype of thyroid cancer. A systems biology approach to PTC can elucidate the mechanism by which molecular components work and interact with one another to decipher a panoramic view of the pathophysiology. PTC associated genes and transcriptomic data were retrieved from DisGeNET and Gene Expression Omnibus database respectively. Published proteomic and metabolomic datasets in PTC from EMBL-EBI were used. Gene Ontolo...
• Evidence snippets:
• Snippet 1 (score: 0.496) > Papillary thyroid cancer (PTC) is the most prevalent follicular cell-derived subtype of thyroid cancer. A systems biology approach to PTC can elucidate the mechanism by which molecular components work and interact with one another to decipher a panoramic view of the pathophysiology. PTC associated genes and transcriptomic data were retrieved from DisGeNET and Gene Expression Omnibus database respectively. Published proteomic and metabolomic datasets in PTC from EMBL-EBI were used. Gene Ontology and pathway analyses were performed with SNPs, differentially expressed genes (DEGs), proteins, and metabolites linked to PTC. The effect of a nucleotide substitution on a protein's function was investigated. Additionally, significant transcription factors (TFs) and kinases were identified. An integrated strategy was used to analyse the multi-omics data to determine the key deregulated pathways in PTC carcinogenesis. Pathways linked to carbohydrate, protein, and lipid metabolism, along with the immune response, signaling, apoptosis, gene expression, epithelial–mesenchymal transition (EMT), and disease onset, were identified as significant for the clinical and functional aspects of PTC. Glyoxylate and dicarboxylate metabolism and citrate cycle were the most common pathways among the PTC omics datasets. Commonality analysis deciphered five TFs and fifty-seven kinases crucial for PTC genesis and progression. Core deregulated pathways, TFs, and kinases modulate critical biological processes like proliferation, angiogenesis, immune infiltration, invasion, autophagy, EMT, and metastasis in PTC. Identified dysregulated pathways, TFs and kinases are critical in PTC and may help in systems level understanding and device specific experiments, biomarkers, and drug targets for better management of PTC.

[6] Association of CYP2D6*4 gene polymorphism with early papillary thyroid carcinoma

• Authors: Aynur Dağlar Aday, T. Öztürk, Başak Akadam Teker, F. Aksoy, H. Aydogan et al.
• Year: 2021
• Venue: Turkish Journal of Biochemistry
• URL: https://www.semanticscholar.org/paper/db3c0cf5196ebfc63ae9fafe575afc3ad519f7c0
• DOI: 10.1515/tjb-2020-0103
• Citations: 2
• Summary: The findings indicate that the poor metabolizer CYP2D6*4 genotype may be a risk factor, especially in early PTC development.
• Evidence snippets:
• Snippet 1 (score: 0.491) > Although thyroid carcinomas constitute only 1% of all malignancies in humans; they are responsible for more than 90% of all endocrine cancers [1]. The majority of thyroid cancers are epithelial tumors that arise from thyroid follicular cells. They are mainly classified into three subtypes: papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC) and anaplastic thyroid carcinoma (ATC). Differently, medullary thyroid carcinoma (MTC) derives from thyroid parafollicular (C) cells [2]. > PTC, the commonest type of endocrine malignancy, is a differentiated cancer and its incidence has risen a lot in recent decades [3]. PTC is classified into three major variants. Those are classic (CVPTC), follicular (FVPTC) and tall cell variants (TCVPTC). The genetic alterations of the signaling proteins in the mitogen-activated protein kinase (MAPK) pathway, including RET, ALK, RAS and BRAF are closely related with PTC [4]. Many additional tests used together with thyroid specimens have focused on biomarkers in this signaling pathway [5]. Although more advanced molecular tests are convenient, BRAF mutation is the most crucial biomarker for the diagnosis of PTC [6]. The molecular mechanisms that participate in PTC tumorigenesis and progression are not fully understood. Thus, elucidation of the underlying molecular mechanisms will be useful for the advancement of new diagnosis and treatment strategies for PTC. > Cytochrome P450s (CYPs) are mostly located in the liver and metabolize xenobiotics to non-toxic or carcinogenic metabolites [7]. CYP2D6 (debrisoquine hydroxylase) is a member of CYP family and the CYP2D6 gene takes place on chromosome 22q13.1 [8]. CYP2D6, takes part in the metabolism of drugs and bioactivation of several procarcinogens and neurotoxins [9].

[7] Identification of Hub Genes in Anaplastic Thyroid Carcinoma: Evidence From Bioinformatics Analysis

• Authors: Liqi Li, Mingjie Zhu, Hu Huang, Junqiang Wu, D. Meng
• Year: 2020
• Venue: Technology in Cancer Research & Treatment
• URL: https://www.semanticscholar.org/paper/080dbb6867eca7b73ad5b6e5accb4e2bdcdae280
• DOI: 10.1177/1533033820962135
• PMID: 33025856
• PMCID: 7545761
• Citations: 10
• Summary: Several key genes are identified that may play key roles in ATC development and could serve as prognostic biomarkers or therapeutic targets and provide novel insights into the understanding of the molecular mechanisms of A TC development.
• Evidence snippets:
• Snippet 1 (score: 0.490) > 3][4] ATC arises from the follicular cells of the thyroid gland. However, compared to papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC), ATC cells do not retain any of the biological features of normal follicular cells. 5 Clinically, ATC is characterized by aggressive local disease, high rates of metastasis, and extremely high mortality. 6,7 ased on this, there is an urgent need to further understand the unique biology and pathogenesis underlying this life-threatening disease. > During the last few decades, the clinical and molecular heterogeneity of ATC has been widely recognized, and much effort has been devoted to elucidating the mechanisms underlying this disease. To date, an increasing number of studies have suggested that the tumorigenesis of ATC is a stepwise dedifferentiation that involves the accumulation of somatic pro-carcinogenic mutations in genes such as TP53 and those involved in the PI3K-AKT-mTOR pathway 8,9 ; it has been widely established that BRAF V600E and RAS mutations are common drivers of this disease. 10,11 The current accepted hypothesis is that ATCs are driven from papillary thyroid carcinomas through the acquisition of a discrete number of genomic alterations. 12,13 8][19][20] Although many important drivers have been discovered through genomic and transcriptomic studies, the molecular mechanisms underlying ATC have still not been fully elucidated. > Based on this, we performed a series of bioinformatics analyses in an attempt to identify differentially expressed genes (DEGs) in ATC that are distinct from those in normal thyroid samples by analyzing datasets that were obtained from the Gene Expression Omnibus (GEO) database; we also explored the potential bio-functions through the use of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Furthermore, a protein-protein interaction (PPI) network was constructed, and 7 hub genes were identified based on this network. The results of our present study may provide new insights into the understanding of the molecular mechanisms of ATC development.

[8] Identification of Differentially Expressed Kinase and Screening Potential Anticancer Drugs in Papillary Thyroid Carcinoma

• Authors: Huairong Zhang, B. Gao, B. Shi
• Year: 2016
• Venue: Disease Markers
• URL: https://www.semanticscholar.org/paper/d6ea4f8f45c27aec5e4517c5a9390fe2315dd1fe
• DOI: 10.1155/2016/2832980
• PMID: 27703281
• PMCID: 5040815
• Citations: 4
• Influential citations: 1
• Summary: SRC, MAPK, and EGFR were the most important differentially expressed kinases in PTC and combined inhibitors may have high efficacy in P TC treatment by targeting these kinases.
• Evidence snippets:
• Snippet 1 (score: 0.485) > It is protein kinases that function as core in signaling pathways participating in tumor proliferation, invasion, metastasis, and tumor microenvironment formation in major types of tumors, including thyroid cancer pathogenesis. > It has been identified that in papillary thyroid carcinoma several molecular changes exist: rearranged during transfection (RET)/papillary thyroid carcinoma gene rearrangements, BRAF (B-RAF protooncogene, serine/threonine kinase) gene mutations, RAS (rat sarcoma) mutations, and vascular endothelial growth factor receptor 2 angiogenesis 2 Disease Markers pathways activation. BRAF oncogene mutation occurred in approximately 45% to 70% of patients with papillary thyroid carcinoma and VEGF overexpression is frequently found in tumors that originated in the thyroid [8][9][10][11]. In the landmark DECISION study, Sorafenib, a multikinase inhibitor of RET/RAS/RAF pathway, VEGF receptors 2 and 3, improved the progression-free survival by 3 months, from 5.8 months to 10.8 months, compared with placebo [12]. It emerged as a potentially effective option and approved by Food and Drug Administration (FDA) as a receptor tyrosine kinase inhibitor as treatment of differentiated thyroid cancer refractory to RAI. > We aimed to investigate the protein kinase expression difference between papillary thyroid carcinoma and normal thyroid and possible molecular mechanisms underlying PTC. We try to provide valuable information on PTC associated protein kinases for potential therapeutic targets.

[9] Identification of genes associated with lymph node metastasis in papillary thyroid carcinoma by weighted gene co-expression network analysis

• Authors: Zhen Liu, Mingyue Guo, Lidong Wang, Chenxi Liu, Yongliang Huang
• Year: 2020
• Venue: Unknown venue
• URL: https://www.semanticscholar.org/paper/9bd1ef8de46a1fde714e0e281dd9604b8d8b27cb
• DOI: 10.21203/rs.2.23820/v1
• Summary: The differential genes are screened by combining the datasets of TCGA, GEO and Oncomine in TC for the first time, which makes the screened differential genes have more biological significance.
• Evidence snippets:
• Snippet 1 (score: 0.484) > Thyroid cancer (TC) is a very frequent endocrine system malignant tumor. In recent years, its incidence is increasing year by year, and is generally younger [1]. The most common histological and pathological classification of TC is papillary thyroid carcinoma (PTC), accounting for 80% of all TC [2]. > However, although the growth of PTC is slow and most of the patients is a real good prognosis, there will be some patients with poor surgical results and insensitive to drug treatment, resulting in recurrence or metastasis or even death [3]. Researchers use genetic analysis to study the molecular mechanism of TC to explore the process of TC transfer. In the course of continuous exploration, many new genes related to the TC have been found [4][5][6]. However, at present, the understanding of the molecular mechanism of PTC is not certain. Despite the fact that many genes have clearly played an important role in the occurrence and development of PTC, cancer metastasis is a complex process, which is the result of the interaction of multiple genes. For example, mutation activation of Ras gene is the most classical gene mutation in TC. Because Ras gene is closely related to the classical signal pathway-PI3K/Akt signal pathway, it controls many cellular processes, such as cell growth, proliferation and survival, cell metabolism and autophagy [7]. The mutations of BRAF, RAS and RET-PTC fusion genes in the activated state can cause the activation of MAPK signal pathway, and the activation of p38MAPK/ERK signal transduction pathway will lead to cell proliferation and increase the apoptosis, autophagy and invasion of TC cells [8]. The study of the interaction between genes is more helpful for us to continue to explore the molecular mechanism of PTC. > Weighted co-expression network analysis (WGCNA) is a systems biology method used to describe gene association patterns among different samples. It can be used to establish highly synergistic gene sets, and to identify candidate biomarker genes or therapeutic targets according to the interconnectedness of gene sets and the association between gene sets and phenotypes.

[10] Molecular Alterations in Thyroid Cancer: From Bench to Clinical Practice

• Authors: E. Tirrò, F. Martorana, Chiara Romano, S. Vitale, G. Motta et al.
• Year: 2019
• Venue: Genes
• URL: https://www.semanticscholar.org/paper/d1ff1d9e8131c2446837add86af2de83c66ef8f6
• DOI: 10.3390/genes10090709
• PMID: 31540307
• PMCID: 6771012
• Citations: 87
• Influential citations: 6
• Summary: The genomic alterations and biological processes intertwined with thyroid cancer development are described, also providing a thorough overview of targeted drugs already tested or under investigation for these tumors.
• Evidence snippets:
• Snippet 1 (score: 0.484) > As thyroid cancer progresses, the accumulation of molecular alterations disrupting multiple normal cell functions results in RAIR development, due to impaired NIS expression [23][24][25].Indeed, dysregulation of different receptor-tyrosine kinase (RTK)-dependent signaling and proliferation pathways-such as the mitogen-activated protein kinase (MAPK), the phosphoinositide 3 kinase (PI3K), the Wingless/Integrated (WNT), the p53 and p73 pathways-are involved in the multistep tumorigenic process of thyroid cancer [25][26][27] (Figure 1).Alterations of these cascades can be linked to different mechanisms, including genetic and epigenetic modifications in pathway receptors and effectors [28,29].Moreover, distinct, mutually exclusive molecular alterations may be associated with specific disease stages or histotypes [30]. > Figure 1.Genetic events involved in thyroid carcinogenesis.Papillary thyroid carcinomas (PTC), follicular thyroid carcinomas (FTC) and anaplastic thyroid carcinomas (ATC) originate from thyroid follicular cells and are characterized by molecular alterations (mutations, deletions, gene fusions) involving genes and proteins impinging upon different cellular pathways.The transition from PTC/FTC to poorly differentiated (PDTCs) and ATCs is attributed to additional molecular alterations.Medullary thyroid carcinoma (MTC) originates from para-follicular C-cells and is prevalently characterized by RET or RAS mutations. > In order to better classify the molecular alterations detected in thyroid cancer, we will initially discuss RTK-related upstream signaling pathways involved in tumorigenesis and subsequently focus on the effectors of these pathways.Finally, we will describe alterations contributing to thyroid carcinogenesis that involve pivotal cellular functions.In order to better classify the molecular alterations detected in thyroid cancer, we will initially discuss RTK-related upstream signaling pathways involved in tumorigenesis and subsequently focus on the effectors of these pathways.Finally, we will describe alterations contributing to thyroid carcinogenesis that involve pivotal cellular functions.

[11] Telomerase reverse transcriptase induced thyroid carcinoma cell proliferation through PTEN/AKT signaling pathway

• Authors: Hao Zhang, Ning Hu
• Year: 2018
• Venue: Molecular Medicine Reports
• URL: https://www.semanticscholar.org/paper/d55f3824298aceb87e57be03aa068b50d4eb8c54
• DOI: 10.3892/mmr.2018.9119
• PMID: 29901196
• PMCID: 6072153
• Citations: 12
• Influential citations: 1
• Summary: TERT could induce thyroid carcinoma cell proliferation mainly through the PTEN/AKT signaling pathway according to the molecular mechanisms.
• Evidence snippets:
• Snippet 1 (score: 0.476) > Thyroid carcinoma is the most common endocrine malignant tumor in the world, which accounts for 94.5% of all endocrine tumors. The incidence of thyroid cancer has been increasing since the end of last century and has ranked the top of the list of head and neck cancers (1,2). Papillary thyroid cancer (PTC) is the most common pathology type in thyroid cancer, ~90% of thyroid carcinoma. 85-90% incidence of thyroid cancer was caused by PTC. More women are involved in it than men, and most of them are accompanied by cervical lymph node metastasis. PTC is a low-grade malignancy, the main clinical symptoms of which are the slow growth of thyroid mass and multifocal occurrence, tendency of regional lymph nodes metastasis. The prognosis of PTC is good after proper effective treatment, with 5-year survival rate of 95%, and 10-year survival rate of above 90% (3). However, some PTC is of high invasion ability, and some of them has the tendency of dedifferentiation to form low-differentiated or non-differentiated cancers and result in the decreasing of survival rate and life quality (4). > The occurrence and development of thyroid cancer is a complicated process including a variety of oncogenes, signaling pathway and aberrant proteins, resulting in abnormal proliferation and mutation. Therefore, study on PTC molecular mechanism will help looking for new biomarkers for PTC early diagnosis, lymph nodes metastasis prediction, treatment and prognosis. > Telomerase is a self-templated reverse transcriptase, containing two subunits of TERC (telomerase RNA component) and TERT (telomerase reverse transcriptase). As the Telomerase reverse transcriptase induced thyroid carcinoma cell proliferation through PTEN/AKT signaling pathway core subunit of telomerase, TERT catalyzes TERC reverse transcription to regulate telomerase activity and maintain telomere length (5)(6)(7). Over-expression of TERT could promote the proliferation of mesenchymal stem cells, epithelial cells and nerve cells (8,9).

[12] Growth‐associated protein 43 promotes thyroid cancer cell lines progression via epithelial‐mesenchymal transition

• Authors: C. Zheng, Rui-da Quan, Chen-Yong Wu, Jing Hu, Bangyi Lin et al.
• Year: 2019
• Venue: Journal of Cellular and Molecular Medicine
• URL: https://www.semanticscholar.org/paper/d73055efdaacac199d65ba868c199f4732ca21cc
• DOI: 10.1111/jcmm.14460
• PMID: 31568662
• PMCID: 6850924
• Citations: 15
• Summary: GAP43 is a gene which was associated with PTC and might be a potential therapeutic target and it is indicated that GAP43 could modulate the expression of epithelial‐mesenchymal transition‐related proteins, which could influence invasion and migration.
• Evidence snippets:
• Snippet 1 (score: 0.474) > Thyroid cancer (TC) is maintaining at a high incidence level and it becomes one of the most common cancers in worldwide. 1,2 The US National Cancer Institute anticipated 53 990 new cases besides 2110 death numbers of patients because of TC in the USA in 2018. 3,4 sides, the papillary thyroid cancer (PTC) is the commonest subtype of TC (accounts for 80%-90%). 5 Although the incidence of PTC is high, it is generally considered that PTC is relatively curable and has a good prognosis. 6,7 After a surgical operation or radio-iodinated therapy, patients with PTC show satisfactory prognosis besides a general 10-year survival rate of 90%. 7 However, clinical course of PTC usually follows indolent and carries excellent prognosis, it is still highly metastatic and relapses after routine treatment. 5 ][10] LNM has been shown to occur in approximately 20% of all PTC patients, and regional recurrence occurred in 10% of patients undergoing total thyroidectomy. 11 So, it is vital for us to facilitate the in-depth investigation of the mechanism of PTC and help doctors to provide an appropriate treatment approach. > The incidence and development of PTC are primarily affected by genomic alternation, involving stimulation of oncogene and silencing of a tumour suppressor gene. Accumulating reports have been published about molecular mechanisms of PTC over nearly a period of 20 years. B-type Raf kinase (BRAF) V600E, a famous gene mutation, promotes PTC tumorigenesis and progression by abnormally stimulating the mitogen-activated pathway kinase pathway. 12 Besides, some notable mutations such as RAS mutation, 13 TERT mutation, 14 PTEN mutation, 15 PIK3CA mutation 16,17 and TP53 mutation 18 also show a significant part in thyroid carcinoma. Numerous researchers have made remarkable progress in TC gene research, but many characters of PTC are yet relatively unspecified. Hence, examining for new potential markers and clarifying molecular mechanisms in the improvement of thyroid carcinoma is still essential. > In our previous study, we have conducted next-generation of 19 pairs of PTC tissues and adjacent normal thyroid tissue. 19

[13] High Genetic Diversity and No Evidence of Clonal Relation in Synchronous Thyroid Carcinomas Associated with Hashimoto’s Thyroiditis: A Next-Generation Sequencing Analysis

• Authors: C. Molnár, E. Bádon, A. Mokánszki, A. Mónus, L. Beke et al.
• Year: 2020
• Venue: Diagnostics
• URL: https://www.semanticscholar.org/paper/935eb885fe76e6735a9baf1789f52742ec570f53
• DOI: 10.3390/diagnostics10010048
• PMID: 31963551
• PMCID: 7167801
• Citations: 9
• Summary: The different BRAF statuses in coincident thyroid carcinoma foci within the same organ outline a special challenge for molecular follow-up and therapeutic decision-making.
• Evidence snippets:
• Snippet 1 (score: 0.471) > Thyroid carcinoma is the most frequent endocrine neoplasia, the incidence of which is increasing worldwide [1,2]. Major etiological factors include environmental and direct thyrotoxic effects, and selected comorbidities such as autoimmune thyroid disease are also considered as associated factors [3,4]. While the immunological background and pathological consequences of autoimmune lymphocytic thyroiditis and, more recently, IgG4-related chronic inflammation have been gradually elucidated, the exact mechanisms of subsequent carcinogenesis are mostly unknown. Hashimoto's thyroiditis (HT) is one of the most frequent autoimmune thyroid disorders characterized by massive lymphocytic infiltrate and progressive destruction of the thyroid parenchyma [5,6]. The autoimmune attack results in direct cellular toxicity, and regeneration is associated with endocrine and metabolic/oxidative stress at the level of the thyroid follicular epithelium [7,8]. Parenchymal hypofunction, on the other hand, triggers a constant proliferative stimulus by thyroid-stimulating hormone (TSH), enabling increased survival and adaptive selection, which are both important factors in the process of carcinogenesis. According to the current view, not only has the association between HT and especially papillary-type thyroid carcinoma (PTC) been established, but the frequent multifocality of PTC can also be explained by HT-related injury and consequent stimulatory mechanisms [6,9]. > With the recent developments of genomic DNA testing, a sharpened picture of relevant gene alterations and molecular pathways can also be provided for thyroid malignancies. The availability of next-generation sequencing (NGS) approaches enables the large-scale analysis of cancer genotype from archived pathological material [10,11]. Several well-documented studies using NGS were performed to define the mutational spectrum of thyroid carcinoma, especially focusing on advanced and anaplastic carcinoma cohorts [12,13]. Data obtained by extended cancer-related gene panel analysis delineated MAPK and PI3K pathway mutations as contributing to aggressive behavior.

[14] Genome-wide expression analysis suggests a crucial role of dysregulation of matrix metalloproteinases pathway in undifferentiated thyroid carcinoma

• Authors: J. Espinal-Enríquez, S. Muñoz-Montero, Ivan Imaz-Rosshandler, Aldo Huerta-Verde, Carmen Mejía et al.
• Year: 2015
• Venue: BMC Genomics
• URL: https://www.semanticscholar.org/paper/aaf44d01ab95964e2cee2acee8339ddf6bd039c7
• DOI: 10.1186/s12864-015-1372-0
• Summary: The genome-wide analysis of thyroid carcinoma subtypes emphasizes the preponderance of pathway-dysregulation mechanisms over simple gene-malfunction as the main mechanism involved in the development of a cancer phenotype.
• Evidence snippets:
• Snippet 1 (score: 0.471) > Thyroid cancer (TC) is the most common malignant cancer of the Endocrine System. Histologically, there are three main subtypes of TC: follicular, papillary and anaplastic. Diagnosing a thyroid tumor subtype with a high level of accuracy and confidence is still a difficult task because genetic, molecular and cellular mechanisms underlying the transition from differentiated to undifferentiated thyroid tumors are not well understood. A genome-wide analysis of these three subtypes of thyroid carcinoma was carried out in order to identify significant differences in expression levels as well as enriched pathways for non-shared molecular and cellular features between subtypes. Inhibition of matrix metalloproteinases pathway is a major event involved in thyroid cancer progression and its dysregulation may result crucial for invasiveness, migration and metastasis. This pathway is drastically altered in ATC while in FTC and PTC, the most important pathways are related to DNA-repair activation or cell to cell signaling events. A progression from FTC to PTC and then to ATC was detected and validated on two independent datasets. Moreover, PTX3, COLEC12 and PDGFRA genes were found as possible candidates for biomarkers of ATC while GPR110 could be tested to distinguish PTC over other tumor subtypes. The genome-wide analysis emphasizes the preponderance of pathway-dysregulation mechanisms over simple gene-malfunction as the main mechanism involved in the development of a cancer phenotype.

[15] Nasopharyngeal Carcinoma Signaling Pathway: An Update on Molecular Biomarkers

• Authors: W. Tulalamba, T. Janvilisri
• Year: 2012
• Venue: International Journal of Cell Biology
• URL: https://www.semanticscholar.org/paper/307cb9186444d9dad6e2e3b53763be0de76de186
• DOI: 10.1155/2012/594681
• PMID: 22500174
• PMCID: 3303613
• Citations: 93
• Influential citations: 5
• Summary: The molecular signaling pathways in the NPC are discussed for the holistic view of NPC development and progression and the important insights toward NPC pathogenesis may offer strategies for identification of novel biomarkers for diagnosis and prognosis.
• Evidence snippets:
• Snippet 1 (score: 0.470) > In the pregenomic eras, highly integrated and complex circuitry of molecular signaling in NPC pathogenesis was only partially understood. Over the past decade, the knowledge of the molecular mechanisms in NPC carcinogenesis has been rapidly accumulated. Dysregulation and abnormal protein expression of molecules in certain signaling pathways involved in cellular functions including proliferation, adhesion, survival, and apoptosis has been demonstrated in the NPC cells. Detailed information on the complex network in signaling pathway leading to a coordinated pattern of gene expression and regulation in NPC will undoubtedly provide important clues to develop novel prognostic and therapeutic strategies for this cancer. Refining molecular markers into clinically relevant assays may assist in the detection of NPC in asymptomatic patients, as well as stage classification and monitoring disease progression and treatments. Furthermore, selective regulation of particular proteins targeting cancer cell proliferation, invasion, and apoptosis is a hopeful prospect for future anticancer therapy that slow disease progression and improve survival.

[16] Bioinformatics analysis to screen key genes in papillary thyroid carcinoma

• Authors: Yuanhu Liu, Shuwei Gao, Yaqiong Jin, Yeran Yang, J. Tai et al.
• Year: 2019
• Venue: Oncology Letters
• URL: https://www.semanticscholar.org/paper/b24ecef22e13d5187ed1c036d514bbd3f2af07ec
• DOI: 10.3892/ol.2019.11100
• PMID: 31897130
• PMCID: 6924100
• Citations: 15
• Summary: The findings of the present study suggest that these genes and related pathways are involved in key events of PTC progression and facilitate the identification of prognostic biomarkers.
• Evidence snippets:
• Snippet 1 (score: 0.462) > Papillary thyroid carcinoma (PTC) is the most common type of thyroid carcinoma, and its incidence has been on the increase in recent years. However, the molecular mechanism of PTC is unclear and misdiagnosis remains a major issue. Therefore, the present study aimed to investigate this mechanism, and to identify key prognostic biomarkers. Integrated analysis was used to explore differentially expressed genes (DEGs) between PTC and healthy thyroid tissue. To investigate the functions and pathways associated with DEGs, Gene Ontology, pathway and protein-protein interaction (PPI) network analyses were performed. The predictive accuracy of DEGs was evaluated using the receiver operating characteristic (ROC) curve. Based on the four microarray datasets obtained from the Gene Expression Omnibus database, namely GSE33630, GSE27155, GSE3467 and GSE3678, a total of 153 DEGs were identified, including 66 upregulated and 87 downregulated DEGs in PTC compared with controls. These DEGs were significantly enriched in cancer-related pathways and the phosphoinositide 3-kinase-AKT signaling pathway. PPI network analysis screened out key genes, including acetyl-CoA carboxylase beta, cyclin D1, BCL2, and serpin peptidase inhibitor clade A member 1, which may serve important roles in PTC pathogenesis. ROC analysis revealed that these DEGs had excellent predictive performance, thus verifying their potential for clinical diagnosis. Taken together, the findings of the present study suggest that these genes and related pathways are involved in key events of PTC progression and facilitate the identification of prognostic biomarkers.

[17] The potential role of reprogrammed glucose metabolism: an emerging actionable codependent target in thyroid cancer

• Authors: Sai-Li Duan, Min Wu, Zhe-Jia Zhang, Shi Chang
• Year: 2023
• Venue: Journal of Translational Medicine
• URL: https://www.semanticscholar.org/paper/848fc3da01105356f5b19f4b99e3b42e0d89f78d
• DOI: 10.1186/s12967-023-04617-2
• PMID: 37853445
• PMCID: 10585934
• Citations: 20
• Influential citations: 1
• Summary: Past and recent advances in the understanding of the reprogramming of glucose metabolism in thyroid cancer cells are summarized, which are expected to yield new therapeutic approaches for patients with special pathological types of thyroid cancer by targeting reprogrammed glucose metabolism.
• Evidence snippets:
• Snippet 1 (score: 0.461) > Thyroid cancer (TC) is an endocrine system tumor originating from follicular thyroid cells and parafollicular C cells, and its incidence rate is rising worldwide [1,2].Most thyroid malignancies (> 95%) are differentiated thyroid cancers (DTCs), which include papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC) [3].Lymph node metastasis is a common clinical feature of DTC, and a considerable portion of DTC is prone to early cervical lymph node metastases (approximately 20-70%), which is an important factor affecting the prognosis of DTC patients [4,5].Despite the widespread use of multimodality treatment (ie, surgery, chemotherapy, and radiotherapy), survival rates have not improved much over the past few decades, suggesting that new treatment options should be explored [6][7][8].Therefore, we recommend seeking other effective treatments for TC.Probing the molecular mechanism of disease progress, and developing new targeted drugs remain the focus of TC research [9].Initiation and progression of TC involves multiple genetic and epigenetic alterations, among which common mutations found in TC are point mutations in the BRAF and RAS genes as well as RET/PTC and PAX8/ PPARγ chromosomal rearrangements [10,11].These alterations often lead to anomalies in the proliferation, Page 2 of 20 Duan et al. Journal of Translational Medicine (2023) 21:735 differentiation and metabolism patterns of thyroid follicular cells, acting synergistically to amplify their effects on thyroid tumor development.These mutations are crucial for the abnormal activation of the MAPK and PI3K-AKT signaling pathways, which primarily regulate cell proliferation and differentiation, but also directly regulate the activity of oxidative phosphorylation, cellular glucose uptake and aerobic glycolytic processes [12,13].Cancer cells frequently undergo a reorganization of metabolism to promote growth, survival, proliferation and long-term maintenance [14].

[18] A Comprehensive Risk Assessment and Stratification Model of Papillary Thyroid Carcinoma Based on the Autophagy-Related LncRNAs

• Authors: Yongrun Mu, Fu-Jiang Song, Kai Yuan, Zili Zhang, Yan Lu et al.
• Year: 2022
• Venue: Frontiers in Oncology
• URL: https://www.semanticscholar.org/paper/900b75f99d7ac2d2af53131fe7b7f31d883fbd5a
• DOI: 10.3389/fonc.2021.771556
• PMID: 35284335
• PMCID: 8908373
• Citations: 3
• Summary: A novel risk stratification for PTC based on the expression profiles of autophagy-related lncRNAs is established and knockdown of the CRNDE in PTC increased the sensitivity to sorafenib.
• Evidence snippets:
• Snippet 1 (score: 0.460) > Thyroid carcinoma is the most common endocrine malignant tumor, and 90% of this tumor type is made up of papillary carcinoma histologically (1). The improvement of thyroidbased diagnostic procedures, such as radiographic imaging and fine-needle aspiration, has contributed directly to the rapid increase of new discovered cases (2). Similarly, papillary carcinoma accounts for most of the increase (3). However, the other histological subtypes (anaplastic, medullary, and follicular) do not change markedly (4,5). The sharp increase in mortality due to PTC has garnered increased concern from the public (3,6,7). > With the research on papillary carcinoma mainly focused on genetics, transcriptomics proteomics, and epigenetics, mechanistic knowledge is growing rapidly. Therefore, determining the correlation of the clinicopathological information with the genomic alternations and transcriptome has become a new area of research for many researchers (8). > The increasing risk of small thyroid nodes due to overdiagnosis alone remains controversial among clinical decision makers. Although the eighth edition of the A m e r i c a n J o i n t C o m m i t t e e o n C a n c e r -U n i o n fo r International Cancer Control (AJCC-UICC) staging system describes that most patients at low risk have a lower mortality for differentiated thyroid cancer, there is a crucial discussion about initial therapeutic decision-making and the clinical management of those newly diagnosed (9), especially regarding the requirement for active surveillance or thyroid surgery (1). > Autophagy is a type II programmed cell death process, which directly controls physiological mechanisms by degradation of proteins and organelles to achieve homeostasis (10). It is an important pathway necessary to adjust to various stresses (11). Nevertheless, dysregulation of autophagy involved in multiple diseases, including cancer (12)(13)(14), results in both tumor suppression and oncogenesis at different stages of cancer development.

[19] Let-7a inhibits migration, invasion and tumor growth by targeting AKT2 in papillary thyroid carcinoma

• Authors: Bin Zhou, Hailin Shan, Ying Su, Kai Xia, Runlong Zou et al.
• Year: 2017
• Venue: Oncotarget
• URL: https://www.semanticscholar.org/paper/333d40c672cc41bc465694b23902c219bb61f761
• DOI: 10.18632/oncotarget.19261
• PMID: 29050238
• PMCID: 5642513
• Citations: 27
• Influential citations: 1
• Summary: Findings suggest that let-7a acts as a novel suppressor by targeting the AKT2 gene and might be a candidate target for the development of novel therapeutic strategies to treat papillary thyroid carcinoma.
• Evidence snippets:
• Snippet 1 (score: 0.458) > Thyroid carcinoma is the most common endocrine malignancy of the thyroid in adults [1]. Papillary thyroid carcinoma (PTC), the most prevalent histology subtype (80% of cases), and its incidence have been increased a lot over the past few decades [2,3]. Multifocal lesions are one of clinical characteristics of PTC and provide a power evidence of lymph node invasion and distant metastasis [4,5]. Currently, the invasion and metastasis of PTC are the major cause of fatal outcome and, therefore, it is essential to elucidate the molecular mechanisms of PTC progression to facilitate the development of novel targeted therapies. > MicroRNAs (miRNAs) are non-protein-coding, 19-22 nucleotide RNAs that regulate gene expression posttranscriptionally by targeting their mRNAs, leading to mRNA degradation or inhibition of protein translation [6,7]. MiRNAs include miR-187, -221, -31, -146b are known to play important roles in PTC. In particular, studies showed that expression levels of let-7a are downregulated in many types of cancers, including PTC [8][9][10], but whether its levels are correlated with PTC clinical stages is not known yet. In addition, the roles and mechanisms of let-7a in regulating cell proliferation, migration, invasion and tumorigenesis far from being fully elucidated. > AKT2 (v-AKT murine thymoma viral oncogene homologue 2), a key downstream effector of the phosphatidylinositol 3-kinase(PI3K) pathway [11]. Many studies show that AKT2 is involved in cancer development and play a great role in cell cycle, apoptosis, proliferation and migration [12,13]. Recent studies indicate that AKT2 could be regulated by microRNAs. MiR-137 targeted AKT2 to suppresses tumor growth and metastasis in human hepatocellular carcinoma [14]. MiR-302b inhibited cell cycle in human hepatocellular carcinoma by targeting AKT2 [15].

Notes

• This provider combines search_papers_by_relevance with snippet_search.
• No synthesis or second-stage model call is performed.