scholarly journals The molecular and gene/miRNA expression profiles of radioiodine resistant papillary thyroid cancer

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Carla Colombo ◽  
Emanuela Minna ◽  
Chiara Gargiuli ◽  
Marina Muzza ◽  
Matteo Dugo ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Mirna Expression ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Tissue Type ◽  
Molecular Profile ◽  
Papillary Thyroid ◽  
Primary Tumors ◽  
Disease Persistence

Abstract Background Papillary thyroid cancer (PTC) is the most frequent endocrine tumor. Radioiodine (RAI) treatment is highly effective in these tumors, but up to 60% of metastatic cases become RAI-refractory. Scanty data are available on either the molecular pattern of radioiodine refractory papillary thyroid cancers (PTC) or the mechanisms responsible for RAI resistance. Methods We analyzed the molecular profile and gene/miRNA expression in primary PTCs, synchronous and RAI-refractory lymph node metastases (LNMs) in correlation to RAI avidity or refractoriness. We classified patients as RAI+/D+ (RAI uptake/disease persistence), RAI−/D+ (absent RAI uptake/disease persistence), and RAI+/D- (RAI uptake/disease remission), and analyzed the molecular and gene/miRNA profiles, and the expression of thyroid differentiation (TD) related genes. Results A different molecular profile according to the RAI class was observed: BRAFV600E cases were more frequent in RAI−/D+ (P = 0.032), and fusion genes in RAI+/D+ cases. RAI+/D- patients were less frequently pTERT mutations positive, and more frequently wild type for the tested mutations/fusions. Expression profiles clearly distinguished PTC from normal thyroid. On the other hand, in refractory cases (RAI+/D+ and RAI−/D+) no distinctive PTC expression patterns were associated with either tissue type, or RAI uptake, but with the driving lesion and BRAF−/RAS-like subtype. Primary tumors and RAI-refractory LNMs with BRAFV600E mutation display transcriptome similarity suggesting that RAI minimally affects the expression profiles of RAI-refractory metastases. Molecular profiles associated with the expression of TPO, SLC26A4 and TD genes, that were found more downregulated in BRAFV600E than in gene fusions tumors. Conclusions The present data indicate a different molecular profile in RAI-avid and RAI-refractory metastatic PTCs. Moreover, BRAFV600E tumors displayed reduced differentiation and intrinsic RAI refractoriness, while PTCs with fusion oncogenes are RAI-avid but persistent, suggesting different oncogene-driven mechanisms leading to RAI refractoriness.

scholarly journals Detection of BRAFV600E in Liquid Biopsy from Patients with Papillary Thyroid Cancer Is Associated with Tumor Aggressiveness and Response to Therapy

2020 ◽  
Vol 9 (8) ◽  
pp. 2481
Author(s):  
Kirk Jensen ◽  
Shilpa Thakur ◽  
Aneeta Patel ◽  
Maria Cecilia Mendonca-Torres ◽  
John Costello ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Liquid Biopsy ◽  
Digital Pcr ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Papillary Thyroid ◽  
Primary Tumors ◽  
Promising Tool ◽  
Increased Risk

The detection of rare mutational targets in plasma (liquid biopsy) has emerged as a promising tool for the assessment of patients with cancer. We determined the presence of cell-free DNA containing the BRAFV600E mutations (cfBRAFV600E) in plasma samples from 57 patients with papillary thyroid cancer (PTC) with somatic BRAFV600E mutation-positive primary tumors using microfluidic digital PCR, and co-amplification at lower denaturation temperature (COLD) PCR. Mutant cfBRAFV600E alleles were detected in 24/57 (42.1%) of the examined patients. The presence of cfBRAFV600E was significantly associated with tumor size (p = 0.03), multifocal patterns of growth (p = 0.03), the presence of extrathyroidal gross extension (p = 0.02) and the presence of pulmonary micrometastases (p = 0.04). In patients with low-, intermediate- and high-risk PTCs, cfBRAFV600E was detected in 4/19 (21.0%), 8/22 (36.3%) and 12/16 (75.0%) of cases, respectively. Patients with detectable cfBRAFV600E were characterized by a 4.68 times higher likelihood of non-excellent response to therapy, as compared to patients without detectable cfBRAFV600E (OR (odds ratios), 4.68; 95% CI (confidence intervals)) 1.26–17.32; p = 0.02). In summary, the combination of digital polymerase chain reaction (dPCR) with COLD-PCR enables the detection of BRAFV600E in the liquid biopsy from patients with PTCs and could prove useful for the identification of patients with PTC at an increased risk for a structurally or biochemically incomplete or indeterminate response to treatment.

scholarly journals Alternative mutations of BRAF, RET and NTRK1 are associated with similar but distinct gene expression patterns in papillary thyroid cancer

Oncogene ◽  
2004 ◽  
Vol 23 (44) ◽  
pp. 7436-7440 ◽  
Author(s):  
Milo Frattini ◽  
Cristina Ferrario ◽  
Paola Bressan ◽  
Debora Balestra ◽  
Loris De Cecco ◽  
...  
Keyword(s):  
Gene Expression ◽  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Papillary Thyroid ◽  
Distinct Gene

scholarly journals Downregulation of TSPAN13 by miR-369-3p inhibits cell proliferation in papillary thyroid cancer (PTC)

2018 ◽  
Author(s):  
Peng Li ◽  
Mingqiang Dong ◽  
Zhigang Wang
Keyword(s):  
Cell Proliferation ◽  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Expression Profiles ◽  
Surface Proteins ◽  
The Cancer Genome Atlas ◽  
Luciferase Reporter ◽  
Papillary Thyroid ◽  
Small Interfering Rnas

Previous studies demonstrated dysregulation of different microRNAs in thyroid cancer. Tetraspanins (TSPANs) are cell surface proteins with critical roles in many cellular processes, and implications in tumor development. Here we investigated the role of miR-369-3p in papillary thyroid cancer (PTC) and its association with TSPAN13. miR-369-3p and the TSPAN13 gene expression profiles of 513 thyroid cancer and 59 normal thyroid tissues were downloaded from the Cancer Genome Atlas database. Thyroid cancer tissues were classified according to the histological type, grouped based on low and high median miR-369-3p and TSPAN13 expression, and analyzed in relation to overall survival (OS) of patients. Human PTC cell lines (TPC-1 and GLAG-66) and human embryonic kidney 293T (HEK293T) cells were used for in vitro analysis. Transfection experiments were performed with synthetic miRNA mimics for miR-369-3p and small interfering RNAs for TSPAN13. Relative expression of miR-369-3p and TSPAN13 mRNA was determined by RT-qPCR. Protein levels of TSPAN13 were determined by western blotting. Cell proliferation (CCK-8 assay), colony formation, and apoptosis (flow cytometry) were analyzed in transfected cells. Binding sites of miR-369-3p in TSPAN13 mRNA were determined by bioinformatics analysis and dual luciferase reporter assay. miR-369-3p was downregulated and TSPAN13 upregulated in PTC, follicular thyroid cancer, and tall cell variant tissues. Both low expression of miR-369-3p and high expression of TSPAN13 were associated with shorter OS in thyroid cancer patients. Overexpression of miR-369-3p significantly suppressed proliferation and promoted apoptosis in PTC cells. TSPAN13 was a direct target of miR-369-3p, and silencing of TSPAN13 phenocopied the effect of miR-369-3p mimics in PTC cells. Overall, the downregulation of miR-369-3p and consequent upregulation of its target TSPAN13 appear to be involved in pathophysiology of PTC.

scholarly journals Down-regulation of DANCR acts as a potential biomarker for papillary thyroid cancer diagnosis

2019 ◽  
Vol 39 (4) ◽  
Author(s):  
Ke Zhang ◽  
Jing Lv ◽  
Xiaowei Peng ◽  
Jianqiu Liu ◽  
Cuilin Li ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Expression Profiles ◽  
Expression Level ◽  
Papillary Thyroid ◽  
Normal Tissues ◽  
Cancer Breast ◽  
Tumor Tissues ◽  
Potential Biomarker ◽  
Reverse Transcription Quantitative Pcr

AbstractLong non-coding RNAs (lncRNAs) have been reported to be dysregulated and play a crucial role in the progression of cancer. LncRNA DANCR has recently been revealed to be involved in tumorigenesis of numerous types of cancer, including osteosarcoma, gastric cancer, breast cancer, hepatocellular carcinoma, and colorectal cancer. However, the expression profiles and biological relevance of DANCR in papillary thyroid cancer (PTC) have not yet been reported. In the present study, the expression level of DANCR in PTC tissues and adjacent normal tissues was detected by reverse transcription-quantitative PCR in PTC patients, and then we analyzed the association with clinical pathological characteristics of patients and DANCR expressions. These results demonstrated that the expression of DANCR was notably decreased in tumor tissues in comparison with adjacent normal tissues (P<0.001). Furthermore, the present study found that DANCR expression level was correlated to T grade (P<0.01) and TNM stage (P=0.017). The present study demonstrated that DANCR was associated with PTC aggressive clinical features and may serve as a diagnostic biomarker for detecting PTC patients.

scholarly journals Testicular Orphan Receptor 4 (TR4) Promotes Papillary Thyroid Cancer Invasion via Activating Circ-FNLA/miR-149-5p/MMP9 Signaling

2020 ◽  
Author(s):  
Xiwu Ouyang ◽  
Lemeng Feng ◽  
Lei Yao ◽  
Yao Xiao ◽  
Gewen Zhang ◽  
...  
Keyword(s):  
Cell Migration ◽  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Cell Invasion ◽  
Orphan Receptor ◽  
Clinical Samples ◽  
Mouse Tumor ◽  
Papillary Thyroid ◽  
Primary Tumors ◽  
Incidence And Mortality

Abstract Background: The incidence and mortality of papillary thyroid cancer (PTC) have steadily increased. Although conventional therapies are very effective towards differentiated PTC patients, very limited therapeutic options are applicable to those patients with distant metastases. Therefore, better understanding of the molecular biology of metastatic PTC helps identify novel targets and facilitates the development of new therapies.Methods: Western blot assay was used to check relative gene protein expression. Transwell invasion assay was used to check the invasion capacity of the PTC cells. Wound healing assay was conducted to check the migration capacity of the PTC cells. qRT-PCR assay was used to check relative RNA expression of the cells. IHC assay was used to check TR4 and MMP9 expression in clinical samples or mouse tumor samples. Results: In this study, we first found that testicular orphan receptor 4 (TR4) was significantly increased in PTC tumors spreading to lymph node compared to the paired primary tumors. Experimental evidence suggested that TR4 drove PTC progression via promoting its cell invasion and cell migration. Mechanistically, TR4 transcriptionally regulated the expression level of circ-FLNA, which competed with MMP9 for miR-149-5p binding and led to increased protein level of MMP9. Interruption assays with various gene manipulations verified that TR4/circ-FLNA/miR-149-5p/MMP9 signaling axis played central role in cell invasion and cell migration of PTC cells. Moreover, xenografted mouse model also confirmed that TR4/circ-FLNA signal promoted PTC tumor growth.Conclusions: Overall, our study pinpoints the oncogenic role of TR4 in PTC development and targeting TR4/circ-FLNA/miR-149-5p/MMP9 signaling may be an alternative option for metastatic PTC patients.

scholarly journals Evaluation of the Role of BRAFV600E Somatic Mutation on Papillary Thyroid Cancer Disease Persistence: A Prospective Study

2018 ◽  
Vol 7 (5) ◽  
pp. 251-257 ◽  
Author(s):  
Luca Damiani ◽  
Sabrina Lupo ◽  
Roberta Rossi ◽  
Stefania Bruni ◽  
Mirco Bartolomei ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Prospective Study ◽  
Papillary Thyroid Cancer ◽  
Somatic Mutation ◽  
Papillary Thyroid ◽  
Cancer Disease ◽  
A Prospective Study ◽  
Disease Persistence

scholarly journals Identification of Lipid Metabolism-Related Genes as Prognostic Indicators in Papillary Thyroid Cancer

2021 ◽  
Author(s):  
Shi-Shuai Wen ◽  
Yi Luo ◽  
Wei-Li Wu ◽  
Ting Zhang ◽  
Yi-Chen Yang ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Lipid Metabolism ◽  
Papillary Thyroid Cancer ◽  
Expression Profiles ◽  
Locally Advanced ◽  
Gene Signature ◽  
Structural Basis ◽  
Clinicopathological Parameters ◽  
Papillary Thyroid ◽  
Cox Regression Analysis

Abstract Purpose Lipid metabolism plays important roles not only in the structural basis and energy supply of healthy cells but also in the oncogenesis and progression of cancer. In this study, we investigate the prognostic value of lipid metabolism related genes in papillary thyroid cancer (PTC). Methods The in time to recurrence predictive gene signature was developed, internally and externally validated based on PTC datasets including The Cancer Genome Atlas (TCGA) and GSE33630 datasets. Univariate, LASSO and multivariate Cox regression analysis were applied to assess prognostic genes and build the prognostic gene signature. The expression profiles of prognostic genes were further determined by immunohistochemistry by using in-house cohorts which enrolled 97 patients. Kaplan-Meier curve, time-dependent receiver operating characteristic curve, nomogram and decision curve analysis were used to assess the performance of the gene signature. Results We identified four recurrence-related genes, PDZK1IP1, TMC3, LRP2 and KCNJ13, and established a 4-gene signature recurrence risk model. The expression profile of the 4 genes in the TCGA and in-house cohort indicated that stage T1/T2 PTC and locally advanced PTC exhibited notable associations not only with clinicopathological parameters but also with recurrence. Calibration analysis plots indicated the excellent predictive performance of the prognostic nomogram constructed based on the gene signature. GSEA showed that high-risk cases exhibited changes in several important tumorigenesis-related pathways, such as the intestinal immune network and the p53 and Hedgehog signalling pathways. Conclusion Our findings indicate that lipid metabolism-related gene profiling represents a potential marker for prognosis and treatment decisions for PTC patients.

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