Expression of autophagy-associated proteins in papillary thyroid carcinoma.
Ontology highlight
ABSTRACT:
SUBMITTER: Yang M
PROVIDER: S-EPMC5494896 | biostudies-other | 2017 Jul
REPOSITORIES: biostudies-other
Similar Datasets
Project description:BackgroundFindings of recent studies have demonstrated a rapid increase of the incidence of papillary thyroid carcinoma (PTC), which accounts for nearly 80% of thyroid cancers.ObjectivesThe aim of this study was to explore the association between AXIN2 gene polymorphism and papillary thyroid carcinoma (PTC).Patients and methods106 blood samples (56 PTC patients and 50 healthy controls) were drawn from China-Japan Union Hospital in Jilin province, China, during October 2010 to March 2011. A case-control study was designed to examine the association between AXIN2 and PTC. Seven tag single nucleotide polymorphisms (tag SNPs) in AXIN2 were selected and genotyped. Frequencies of different genotypes and alleles were analyzed between the patients and the controls, using the R × C column contingency table χ(2) test. The possible association of haplotypes constructed by the combined effects of two or more loci with PTC was analyzed through the UNPHASED 3.1.4 program.ResultsRs11655966, rs3923086 and rs7591 of AXIN2 showed significant associations with PTC (P < 0.05). The result of haplotypes analysis showed that rs11655966-rs3923086-rs4791169 had statistically significant differences between the two groups (P < 0.05).ConclusionsTogether with the functions of the target genes, we further elucidated that AXIN2 is associated with papillary thyroid carcinoma in the Chinese Han population.
| S-EPMC4860511 | biostudies-literature
Project description:BackgroundZEB1, a core transcription factor involved in epithelial-mesenchymal transition (EMT), is associated with aggressive cancer cell behavior, treatment resistance, and poor prognosis across various tumor types. Similarly, the expression and activity of CD73, an ectonucleotidase implicated in adenosine generation, is an important marker of tumor malignancy. Growing evidence suggests that EMT and the adenosinergic pathway are intricately linked and play a pivotal role in cancer development. Therefore, this study focuses on exploring the correlations between CD73 and ZEB1, considering their impact on tumor progression.MethodsWe employed CRISPR/Cas9 technology to silence CD73 expression in cell lines derived from papillary thyroid carcinoma. These same cells underwent lentiviral transduction of a reporter of ZEB1 non-coding RNA regulation. We conducted studies on cell migration using scratch assays and analyses of cellular speed and polarity. Additionally, we examined ZEB1 reporter expression through flow cytometry and immunocytochemistry, complemented by Western blot analysis for protein quantification. For further insights, we applied gene signatures representing different EMT states in an RNA-seq expression analysis of papillary thyroid carcinoma samples from The Cancer Genome Atlas.ResultsSilencing CD73 expression led to a reduction in ZEB1 non-coding RNA regulation reporter expression in a papillary thyroid carcinoma-derived cell line. Additionally, it also mitigated ZEB1 protein expression. Moreover, the expression of CD73 and ZEB1 was correlated with alterations in cell morphology characteristics crucial for cell migration, promoting an increase in cell polarity index and cell migration speed. RNA-seq analysis revealed higher expression of NT5E (CD73) in samples with BRAF mutations, accompanied by a prevalence of partial-EMT/hybrid state signature expression.ConclusionsCollectively, our findings suggest an association between CD73 expression and/or activity and the post-transcriptional regulation of ZEB1 by non-coding RNA, indicating a reduction in its absence. Further investigations are warranted to elucidate the relationship between CD73 and ZEB1, with the potential for targeting them as therapeutic alternatives for cancer treatment in the near future.
| S-EPMC10882796 | biostudies-literature
Project description:Papillary thyroid carcinoma (PTC) is a heterogeneous tumor with various histological and molecular subtypes. EHD2 is involved in endocytosis and endosomal recycling. This study aimed to investigate the prognostic significance of EHD2 expression in PTC and develop a new model for predicting persistent/recurrent disease after thyroidectomy. Pathologic slides of 512 consecutive patients with PTC ≥ 1 cm were retrospectively reviewed. BRAF mutation analysis and immunohistochemistry for EHD2 were performed. Clinical significance of EHD2 mRNA expression was analyzed in 388 PTC patients using The Cancer Genome Atlas dataset. The presence of dyscohesive cells and psammoma bodies were found have significant association with persistent/recurrent disease (p = 0.049 and p = 0.038, respectively). The best discrimination of disease-free survival was found by dividing patients into three prognostic groups based on the following two risk factors according to the size category: psammoma bodies ≥ 4 and dyscohesive cells (≥ 1% and ≥ 20% in PTCs of < 2.0 cm and ≥ 2.0 cm, respectively). In PTCs of ≥ 2.0 cm, patients with the two risk factors had a hazard ratio of 13.303 (p = 0.005) compared to those without risk factors. High expression level of EHD2 was associated with BRAF V600E (p < 0.001), presence of dyscohesive cells (p = 0.010), and absence of psammoma bodies (p = 0.001). Increased EHD2 mRNA expression level was associated with extrathyroidal extension (p < 0.001), pT3-4 (p < 0.001), lymph node metastasis (p < 0.001), higher risk of recurrence (p < 0.001), and BRAF V600E (p < 0.001). Our prognostic model is useful for predicting persistent/recurrent disease after surgery of PTC. EHD2 mRNA expression could be a novel prognostic marker for PTC patients.
| S-EPMC5373597 | biostudies-literature
Project description:Papillary thyroid carcinomas (PTC), which is derived from thyroid follicular cells, is the most commonly differentiated thyroid cancer with sex disparity. However, the role of estrogen receptors (ERs) in the pathogenesis of PTC remains unclear. The present study aimed to determine the association of ER mRNA expression levels with clinicopathologic features in PTC. To that aim, the mRNA levels of ESR1 (ERα66), ESR1 (ERα36), ESR2, and G-protein-coupled estrogen receptor 1 (GPER1) in snap-frozen tissue samples from PTCs and adjacent normal thyroid tissues were determined using quantitative reverse transcription polymerase chain reaction (RT-qPCR), and the correlation between ER mRNA expression levels and clinicopathologic features was analyzed. The expression of ERα66, ERα36, ERβ, and GPER1 was lower in PTC specimens than in adjacent normal thyroid tissues. Moreover, low GPER1 expression was associated with extrathyroidal extension. There was no obvious difference in expression of ERs between PTC specimens from male and female patients. In conclusion, our findings highlight the importance of ERs in PTC tumorigenesis.
| S-EPMC8835567 | biostudies-literature
Project description:PAX8 is a thyroid-specific transcription factor whose expression is dysregulated in thyroid cancer. A recent study using a conditional knock-out mouse model identified 58 putative PAX8 target genes. In the present study, we evaluated the expression of 11 of these genes in normal and tumoral thyroid tissues from patients with papillary thyroid cancer (PTC). ATP1B1, GPC3, KCNIP3, and PRLR transcript levels in tumor tissues were significantly lower in PTCs than in NT, whereas LCN2, LGALS1 and SCD1 expression was upregulated in PTC compared with NT. Principal component analysis of the expression of the most markedly dysregulated PAX8 target genes was able to discriminate between PTC and NT. Immunohistochemistry was used to assess levels of proteins encoded by the two most dyregulated PAX8 target genes, LCN2 and GPC3. Interestingly, GPC3 was detectable in all of the NT samples but none of the PTC samples. Collectively, these findings point to significant PTC-associated dysregulation of several PAX8 target genes, supporting the notion that PAX8-regulated molecular cascades play important roles during thyroid tumorigenesis.
| S-EPMC4889154 | biostudies-literature
Project description:Papillary thyroid carcinoma (PTC) is the most common subtype of thyroid cancer; however, the specific genes and signaling pathways involved in this cancer remain largely unclear. The present study analyzed three profile datasets, GSE6004, GSE29265 and GSE60542, which were comprised of 47 PTC and 41 normal thyroid tissue samples, to identify key genes and pathways associated with PTC. Initially, differentially-expressed genes (DEGs) between PTC and normal thyroid tissue were screened using R 3.4.0 (2017-04-21, R Foundation, Vienna, Austria, http://www.R-project.org/). These DEGs were then clustered by gene ontology functional terms and representative signaling pathways. Additionally, specific key gene nodes were filtered out from a constructed protein-protein interaction (PPI) network. The results identified a total of 423 shared DEGs associated with PTC, including 211 upregulated and 212 downregulated genes. These 423 genes were primarily enriched in glycosaminoglycan binding, sulfur compound binding, heparin binding, enzyme activator activity, peptidase activator activity and hsa04512: Extracellular matrix (ECM)-receptor interaction. A total of 21 central node genes were identified as key genes in the PTC disease process including complement factor D (CFD), Collagen Type I α 1 Chain (COL1A1), Extracellular Matrix Protein 1 (ECM1) and Fibronectin 1 (FN1). These genes are involved in protease binding, G-protein coupled receptor binding, extracellular matrix structural constituent and peptidase regulator activity. To conclude, using bioinformatics analysis, the present study identified candidate DEGs and critical pathways in PTC that may improve the current understanding regarding the underlying mechanisms of PTC. These genes and pathways may be used as potential therapeutic targets of PTC in the future.
| S-EPMC6176351 | biostudies-literature
Project description:Papillary thyroid carcinomas are the most common thyroid cancers and constitute more than 70% of thyroid malignancies. The most common etiologic factor is radiation, but genetic susceptibility and other factors also contribute to the development of papillary thyroid carcinoma. The most common variants include conventional, follicular variant and tall cell variant. However, many other uncommon variants have been described including oncocytic, columnar cell, diffuse sclerosing and solid forms. Immunohistochemical staining with TTF-1 and thyroglobulin is very useful in confirming the diagnosis of papillary thyroid carcinoma especially in metastatic sites. Markers such as HBME-1 and CITED1 can assist in separating some difficult cases of follicular variants of papillary thyroid carcinomas from follicular adenomas. Molecular studies have shown that the BRAF V600E mutation is found mainly in papillary and anaplastic thyroid carcinomas. Other molecular markers such as HMGA2 and insulin-like growth factor II mRNA binding protein 3 have been used recently as molecular tests to separate papillary thyroid carcinoma and its variants from follicular adenomas and other benign thyroid nodules.
| S-EPMC3037461 | biostudies-literature
Project description:BackgroundAs a rare but aggressive papillary thyroid carcinoma (PTC) variant, the genetic changes of hobnail variant of PTC (HVPTC) are still unclear.ResultsThe prevalence of HVPTC was 1.69% (18/1062) of all PTC diagnosed in our cohort. 73 samples from 55 patients (17 HVPTC, 26 CPTC, 7 PDTC and 5 ATC) were successfully analyzed using targeted NGS with an 18-gene panel. Thirty-seven mutation variant types were identified among 11 genes. BRAF V600E mutation was the most common mutation, which is present in almost all HVPTC samples (16/17, 94%), most CPTC samples (20/26, 77%), and none of the ATC and PDTC samples. TERT promoter mutation (C228T) was identified in 2 ATC and one HVPTC patient. RAS and TP53 mutation are almost exclusively present among ATC and PDTC samples although TP53 mutation was also observed in 3 HVPTC patients. Six different GNAS mutations were identified among 8 CPTC patients (31%) and none of the HVPTC patients. The only patient who died of disease progression harbored concomitant TERT C228T mutation, BRAF V600E mutation and TP53 mutation.MethodsHVPTC cases were identified from a group of 1062 consecutive surgical specimens diagnosed as PTC between 2000 and 2010. Targeted next-generation sequencing (NGS) was applied to investigate the mutation spectrum of HVPTC, compared to classical PTC (CPTC), poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC).ConclusionAs an aggressive variant of PTC, HVPTC has relatively specific molecular features, which is somewhat different from both CPTC and ATC/PDTC and may underlie its relatively aggressive behavior.
| S-EPMC5400643 | biostudies-literature
Project description:Alterations of the von Hippel-Lindau (VHL) tumor suppressor gene can cause different hereditary tumors associated with VHL syndrome, but the potential role of the VHL gene in papillary thyroid carcinoma (PTC) has not been characterized. This study set out to investigate the relationship of VHL expression level with clinicopathological features of PTC in an ethnically and geographically homogenous group of 264 patients from Serbia, for the first time. Multivariate logistic regression analysis showed a strong correlation between low level of VHL expression and advanced clinical stage (OR = 5.78, 95% CI 3.17-10.53, P<0.0001), classical papillary morphology of the tumor (OR = 2.92, 95% CI 1.33-6.44, P = 0.008) and multifocality (OR = 1.96, 95% CI 1.06-3.62, P = 0.031). In disease-free survival analysis, low VHL expression had marginal significance (P = 0.0502 by the log-rank test) but did not appear to be an independent predictor of the risk for chance of faster recurrence in a proportion hazards model. No somatic mutations or evidence of VHL downregulation via promoter hypermethylation in PTC were found. The results indicate that the decrease of VHL expression associates with tumor progression but the mechanism of downregulation remains to be elucidated.
| S-EPMC4260854 | biostudies-literature
Project description:BACKGROUND:FOXE1, a thyroid-specific transcription factor also known as TTF-2, was recently identified as a major genetic risk factor for papillary thyroid carcinoma (PTC). Its role in thyroid carcinogenesis, however, remains unknown. The purpose of the present study was to assess the relationship between the FOXE1 immunohistochemical features and the clinical and genetic characteristics of PTC. METHODS:Immunohistochemical staining of FOXE1 was performed in 48 PTC cases. Two single nucleotide polymorphisms immediately inside (rs1867277) or in the vicinity (rs965513) of the FOXE1 gene were genotyped by direct sequencing. Histopathological, clinical, and genetic data were included in statistical analyses. RESULTS:FOXE1 exhibited cytoplasmic overexpression in tumor tissue compared to the normal counterpart (p<0.001). Both cancer and normal thyroid cells demonstrated the highest FOXE1 scores in the areas closest to the tumor border (<300 ?m) compared with more distant areas (p<0.001). No differences in FOXE1 staining distributions were found between microcarcinomas and PTC of larger size, between different histopathological variants of PTC, and encapsulated and nonencapsulated tumors. Multivariate regression analysis revealed that nuclear FOXE1 expression in neoplastic cells in the vicinity of the tumor border independently associated with the genotype at rs1867277 (the dominant model of inheritance, p=0.037) and tumor multifocality (p=0.032), and with marginal significance with capsular invasion (p=0.051). CONCLUSIONS:FOXE1 overexpression and translocation to the cytoplasm are phenotypic hallmarks of tumor cells suggesting that FOXE1 is involved in the pathogenesis of PTC. Nuclear FOXE1 expression in tumor cells in the vicinity of the PTC border is associated with the presence of a risk allele of rs1867277 (c.-238G>A) in the 5' untranslated region of the FOXE1 gene, as well as with pathological characteristics of PTC, suggesting possible FOXE1 involvement in the facilitation of tumor development beginning at an early stage.
| S-EPMC3704107 | biostudies-literature