scholarly journals A Novel Nanoproteomic Approach for the Identification of Molecular Targets Associated with Thyroid Tumors

Nanomaterials ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 2370
Author(s):  
María García-Vence ◽  
María del Pilar Chantada-Vázquez ◽  
José Manuel Cameselle-Teijeiro ◽  
Susana B. Bravo ◽  
Cristina Núñez

A thyroid nodule is the most common presentation of thyroid cancer; thus, it is extremely important to differentiate benign from malignant nodules. Within malignant lesions, classification of a thyroid tumor is the primary step in the assessment of the prognosis and selection of treatment. Currently, fine-needle aspiration biopsy (FNAB) is the preoperative test most commonly used for the initial thyroid nodule diagnosis. However, due to some limitations of FNAB, different high-throughput “omics” approaches have emerged that could further support diagnosis based on histopathological patterns. In the present work, formalin-fixed paraffin-embedded (FFPE) tissue specimens from normal (non-neoplastic) thyroid (normal controls (NCs)), benign tumors (follicular thyroid adenomas (FTAs)), and some common types of well-differentiated thyroid carcinoma (follicular thyroid carcinomas (FTCs), conventional or classical papillary thyroid carcinomas (CV-PTCs), and the follicular variant of papillary thyroid carcinomas (FV-PTCs)) were analyzed. For the first time, FFPE thyroid samples were deparaffinized using an easy, fast, and non-toxic method. Protein extracts from thyroid tissue samples were analyzed using a nanoparticle-assisted proteomics approach combined with shotgun LC-MS/MS. The differentially regulated proteins found to be specific for the FTA, FTC, CV-PTC, and FV-PTC subtypes were analyzed with the bioinformatic tools STRING and PANTHER showing a profile of proteins implicated in the thyroid cancer metabolic reprogramming, cancer progression, and metastasis. These proteins represent a new source of potential molecular targets related to thyroid tumors.

2020 ◽  
Vol 23 (6) ◽  
pp. 546-553
Author(s):  
Hongyuan Cui ◽  
Mingwei Zhu ◽  
Junhua Zhang ◽  
Wenqin Li ◽  
Lihui Zou ◽  
...  

Objective: Next-generation sequencing (NGS) was performed to identify genes that were differentially expressed between normal thyroid tissue and papillary thyroid carcinoma (PTC). Materials & Methods: Six candidate genes were selected and further confirmed with quantitative real-time polymerase chain reaction (qRT-PCR), and immunohistochemistry in samples from 24 fresh thyroid tumors and adjacent normal tissues. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was used to investigate signal transduction pathways of the differentially expressed genes. Results: In total, 1690 genes were differentially expressed between samples from patients with PTC and the adjacent normal tissue. Among these, SFRP4, ZNF90, and DCN were the top three upregulated genes, whereas KIRREL3, TRIM36, and GABBR2 were downregulated with the smallest p values. Several pathways were associated with the differentially expressed genes and involved in cellular proliferation, cell migration, and endocrine system tumor progression, which may contribute to the pathogenesis of PTC. Upregulation of SFRP4, ZNF90, and DCN at the mRNA level was further validated with RT-PCR, and DCN expression was further confirmed with immunostaining of PTC samples. Conclusion: These results provide new insights into the molecular mechanisms of PTC. Identification of differentially expressed genes should not only improve the tumor signature for thyroid tumors as a diagnostic biomarker but also reveal potential targets for thyroid tumor treatment.


2014 ◽  
Vol 21 (6) ◽  
pp. 891-902 ◽  
Author(s):  
Min-Hee Kim ◽  
Ja Seong Bae ◽  
Dong-Jun Lim ◽  
Hyoungnam Lee ◽  
So Ra Jeon ◽  
...  

The BRAF V600E mutation is the most common genetic alteration in thyroid cancer. However, its clinicopathological significance and clonal mutation frequency remain unclear. To clarify the inconsistent results, we investigated the association between the allelic frequency of BRAF V600E and the clinicopathological features of classic papillary thyroid carcinoma (PTC). Tumour tissues from two independent sets of patients with classic PTC were manually microdissected and analysed for the presence or absence of the BRAF mutation and the mutant allelic frequency using quantitative pyrosequencing. For external validation, the Cancer Genome Atlas (TCGA) data were analysed. The BRAF V600E mutation was found in 264 (82.2%) out of 321 classic PTCs in the training set. The presence of BRAF V600E was only associated with extrathyroidal extension and the absence of thyroiditis. In BRAF V600E-positive tumours, the mutant allelic frequency varied from 8 to 41% of the total BRAF alleles (median, 20%) and directly correlated with tumour size and the number of metastatic lymph nodes. Lymph node metastases were more frequent in PTCs with a high (≥20%) abundance of mutant alleles than in those with a low abundance of mutant alleles (P=0.010). These results were reinforced by validation dataset (n=348) analysis but were not reproduced in the TCGA dataset. In a population with prevalent BRAF mutations, quantitative analysis of the BRAF mutation could provide additional information regarding tumour behaviour, which is not reflected by qualitative analysis. Nonetheless, prospective studies are needed before the mutated allele percentage can be considered as a prognostic factor.


2020 ◽  
Vol 26 (1) ◽  
pp. 16-21 ◽  
Author(s):  
Ngan Betty Lai ◽  
Dave Garg ◽  
Anthony P. Heaney ◽  
Marvin Bergsneider ◽  
Angela M. Leung

Objective: Acromegaly results from the excessive production of growth hormone and insulin-like growth factor-1. While there is up to a 2-fold increased prevalence of thyroid nodules in patients with acromegaly, the incidence of thyroid cancer in this population varies from 1.6 to 10.6% in several European studies. The goal of our study was to determine the prevalence of thyroid nodules and thyroid cancer among patients with acromegaly at a large urban academic medical center in the United States (U.S.). Methods: A retrospective chart review was performed of all patients with acromegaly between 2006–2015 within the University of California, Los Angeles health system. Data were collected regarding patient demographics, thyroid ultrasounds, thyroid nodule fine needle aspiration (FNA) biopsy cytology, and thyroid surgical pathology. Results: In this cohort (n = 221, 49.3% women, mean age 53.8 ± 15.2 [SD] years, 55.2% Caucasian), 102 patients (46.2%) underwent a thyroid ultrasound, from which 71 patients (52.1% women, mean age 52.9 ± 15.2 [SD] years, 56.3% Caucasian) were found to have a thyroid nodule. Seventeen patients underwent a thyroid nodule FNA biopsy and the results revealed 12 benign biopsies, 1 follicular neoplasm, 3 suspicious for malignancy, and 1 papillary thyroid cancer (PTC), from which 6 underwent thyroidectomy; PTC was confirmed by surgical pathology for all cases (8.5% of all nodules observed). Conclusion: In this sample, the prevalence of thyroid cancer in patients with acromegaly and coexisting thyroid nodules is similar to that reported in the general U.S. population with thyroid nodules (7 to 15%). These findings suggest that there is no benefit of dedicated thyroid nodule screening in patients newly diagnosed with acromegaly. Abbreviations: AACE = American Association of Clinical Endocrinologists; ATA = American Thyroid Association; DTC = differentiated thyroid cancer; FNA = fine needle aspiration; GH = growth hormone; IGF-1 = insulin-like growth factor-1; PTC = papillary thyroid cancer; U.S. = United States


2019 ◽  
Vol 10 (4) ◽  
pp. 3178-3181
Author(s):  
Punitha S ◽  
Vedha pal jeyamani ◽  
Sindhu S ◽  
Bhuvaneshwari P ◽  
Arshath A

Thyroid carcinoma is the majority widespread endocraine malignancy in that papillary thyroid cancer is a well-differentiated type. Since hyperthyroidism protects from thyroid cancer due to lack of reproduction of thyroid tissue by the thyroid-stimulating hormone. The papillary carcinoma is the fast-growing and metastases to local region rapidly. A 60 years old post menopausal women with a known case of hypertension of past 6 years on treatment and with hyperthyroidism of past 2 months was presented in the outpatient department in the hospital with chief complaints of mass in the neck with dyphagia, cough, breathlessness, sense of fullness and odynophagia of past 2 weeks. On physical and general examination patient found with diffuse thyroid swelling with enlarged right sided lymph node. The patient was diagnosed with papillary thyroid caricinoma with various investigation reports includes CT Scan, Immouno history chemistry reports, Histopathology and Two fine-needle aspiration biopsies. The patient has undergone 6 cycles of chemotherapy with the corticosteroids, anti-cancer drugs which includes Vincristine, Cyclophosphamide, Doxorubicin, anti- emetic drugs and also with H2 receptor blockers. The papillary thyroid cancer is common and occurs predominantly in females than in males and with good prognosis and decreased death rates. The higher level of thyroid function is very rare in case of PTC.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Larissa Teodoro ◽  
Karina Colombera Peres ◽  
Matheus Nascimento ◽  
Elisangela Souza Teixeira ◽  
Icleia Siqueira Barreto ◽  
...  

Abstract Thyroid cancer biology is extremely diverse. While some cases never progress clinically or do so indolently, others evolve aggressively and may even lead to death. Cell adhesion molecules are glycoproteins present in the cell membrane and play an important role in inflammatory and neoplastic diseases by recruiting immune cells to these sites. The aim of the present study was to investigate the role of mRNA expression of SELL, ICAM1 and ITGAL in thyroid tumors and their relationship with lymphocyte infiltration. We evaluated by RT-qPCR technique 191 thyroid nodules including 97 benign (79 females, 17 males; 49.8±12.5 years old) and 94 malignant (71 females, 23 males; 48.3±15.5years old) cases. Clinical and pathology data were obtained from 47 goiters; 50 follicular adenomas (FA); 74 papillary thyroid carcinomas (PTC), including: 29 classic papillary thyroid carcinomas (CPTC), 21 follicular variant of PTC (FVPTC), 12oxifilic variant of PTC (OVPTC), 12 tall cell papillary thyroid carcinomas (TCPTC); and 20 follicular thyroid carcinomas (FTC). All patients were managed according to a standard protocol based on current guidelines and followed-up for 78.7±54.2 months. SELL was more expressed in malignant (0.85±1.54 UA) than in benign (0.54±0.71 UA, p=0.0027) nodules. The same occurred with ICAM1 (0.99±1.41 vs. 0.46±0.85, p=0.0001), but not with ITGAL gene expression (1.04±1.63 vs. 0.76±1.21, p=0.2131). In addition, the expression of SELL was different when we compared PTC with FA (0.94±1.62 UA vs. 0.47±0.72 UA, p=0.0018) and FTC with FA (0.82±2.38 UA vs. 0.47±0.72 UA, p=0.0078). ICAM1 expression was lower in goiters (0.46±0.90 UA) when compared with PTC (0.93±1.22 UA, p=0.0030) and FTC (1.03±3.30 UA, p=0.0207). Higher expression of ICAM1 (1.16±3.04 UA vs. 0.52±0.96 UA, p=0.0064) and ITGAL (1.17±1.54 UA vs. 0.49±1.39 UA, p=0.0244) was observed in tumors with lymphocyte infiltrate. Also, ITGAL gene expression was higher in tumors that had distant metastasis at diagnosis (1.53±2.18 UA vs. 0.57±1.10 UA, p=0.0217). We were not able to demonstrate any association between any of the investigated molecules and patients’ outcome. In conclusion, our data suggest that cell adhesion molecules may play an important role in neoplastic thyroid cells proliferation. In addition, our findings show that gene expression of SELL and ICAM1 may assist in the histological characterization of follicular patterned thyroid nodules.


2018 ◽  
Vol 19 (10) ◽  
pp. 2990 ◽  
Author(s):  
Luciana Ferreira ◽  
Raquel Lima ◽  
Ana Bastos ◽  
Andreia Silva ◽  
Catarina Tavares ◽  
...  

Osteopontin (OPN) spliced variants (OPN-SV: OPNa, OPNb, and OPNc) are aberrantly expressed in tumors and frequently associated with cancer progression. This holds true for papillary thyroid carcinoma (PTC), which is the most common type of thyroid cancer (TC). PTC often presents with desmoplasia and dystrophic calcification, including psammoma bodies (PB). This work aimed to investigate total OPN (tOPN) and OPN-SV expression and their association with the presence of PB in the PTC classical variants (cPTC), as well as the involvement of OPN-SV in matrix calcification of TC cell lines. We found that cPTC samples presenting PB showed higher OPN expression levels. In TC cell lines, OPNa overexpression promotes higher matrix calcification and collagen synthesis when compared to that of clones overexpressing OPNb or OPNc. In response to OPN knockdown, calcification was inhibited, paralleled with the downregulation of calcification markers. In conclusion, our data evidenced that OPN expression is associated with the presence of PB in cPTC samples. Among the OPN-SV, OPNa is the main contributor to matrix calcification in tested TC cells, providing clues to a better understanding on the biology and ethiopathogenesis of the calcification process in TC cells.


Sign in / Sign up

Export Citation Format

Share Document