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 ◽  
...  

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.

2019 ◽  
Vol 52 (1) ◽  
Author(s):  
Guangjun Li ◽  
Qingli Kong

Abstract Background Papillary thyroid cancer (PTC) is the most common malignancy of all thyroid cancers. LncRNA LINC00460 has been proved to play roles in the oncogenesis and progression of various tumors, including papillary thyroid cancer. However, the potential molecular mechanism of LINC00460 in PTC is poorly investigated. Results LINC00460 was upregulated in PTC tissues and cells. Raf1 was upregulated in PTC tissues, but miR-485-5p was down-regulated. High LINC00460 expression was associated with poor prognosis. LINC00460 knockdown suppressed proliferation, migration, invation and EMT of PTC cells. Bioinformatics prediction revealed that LINC00460 had binding sites with miR-485-5p, which was validated by luciferase reporter assay. In addition, miR-485-5p was confirmed to directly target Raf1 3′-UTR. Moreover, LINC00460 promoted PTC progression by sponging miR-485-5p to elevate the expression of Raf1. Knockdown of LINC00460 restrained tumor growth in vivo. Conclusion LINC00460 induced proliferation, migration, invation and EMT of PTC cells by regulating the LINC00460/miR-485-5p/Raf1 axis, which indicated that LINC00460 may be a potential biomarker and therapeutic target for PTC.


Author(s):  
Carla Colombo ◽  
Emanuela Minna ◽  
Chiara Gargiuli ◽  
Marina Muzza ◽  
Matteo Dugo ◽  
...  

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.


Author(s):  
Peng Li ◽  
Mingqiang Dong ◽  
Zhigang Wang

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.


2021 ◽  
pp. 153695
Author(s):  
Ye Wang ◽  
Junfu Wang ◽  
Congjun Wang ◽  
Yeyang Chen ◽  
Junqiang Chen

Dose-Response ◽  
2020 ◽  
Vol 18 (2) ◽  
pp. 155932582091933
Author(s):  
Jingyi Zhang ◽  
Dongxia Yan ◽  
Lianping He ◽  
Qing Zhang ◽  
Shuang Wen ◽  
...  

Objective: The aim of this study was to evaluate the levels of caveolin-1 in thyroid follicular epithelial cells of papillary thyroid cancer, follicular thyroid cancer, and nonmalignant thyroid nodule benign follicular adenoma, as well as to explore the relationship between the levels of caveolin-1 and thyroid function. Methods: Thirty cases of papillary thyroid cancer, 10 cases of follicular thyroid cancer, 32 cases of nonmalignant thyroid nodule benign follicular adenoma, and 30 controls were enrolled in this study. Caveolin-1 expression in tissue specimens obtained from these cases was evaluated by immunohistochemistry and Western blotting. Results: Caveolin-1 expression in thyroid epithelial cells of patients with papillary thyroid cancer, particularly female patients, was significantly higher than that in patients with follicular thyroid cancer and nonmalignant thyroid nodule benign follicular adenoma ( P < .005). Serum thyroid-stimulating hormone (TSH) levels in the caveolin-1-positive expression group were lower than that in the caveolin-1-negative expression group, and the lowest expression of caveolin-1 was detected in tissues of patients with Graves’ disease. The serum TSH level was associated with caveolin-1 expression in thyroid epithelial cells. Conclusion: Caveolin-1 may participate in regulating thyroid function and is a potential biomarker of follicular thyroid cancer.


2021 ◽  
Author(s):  
Shi-Shuai Wen ◽  
Yi Luo ◽  
Wei-Li Wu ◽  
Ting Zhang ◽  
Yi-Chen Yang ◽  
...  

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.


2020 ◽  
Author(s):  
Xiao-Jing Qin ◽  
Xu Lin ◽  
Gang Xue ◽  
Hui-Li Fan ◽  
Hao-Yu Wang ◽  
...  

Background: In recent years, the annual incidence of thyroid cancer (TC) has increased, with papillary thyroid cancer (PTC) identified as the most common pathological type accounting for about 80% of all thyroid cancer cases. The tumor microenvironment is known to play a vital role in tumor information transmission and immune detection. Methods: In this study, we examined gene expression data from 518 patients with PTC. The ESTIMATE algorithm was used to calculate immune and stromal scores of PTC patients. Based on a protein-protein interaction (PPI) network, functional enrichment and overall survival analyses, C-X-C motif chemokine ligand 10 (CXCL10) was identified as a core gene. We further investigated the roles of core genes of PTC in the tumor immune microenvironment using LinkedOmics, GSEA, and TIMER tools. Results: Immune, stromal and ESTIMATE scores were related to clinicopathological variables of patients with PTC, but not survival outcomes. Eight differentially expressed genes (DEGs) were associated with survival outcome. In addition, immunochemical staining experiments revealed lower expression of CXCL10 in PTC than paracancerous tissues. GSEA pathway enrichment analysis revealed downregulation of CXCL10 in multiple cancer pathways. CXCL10 and related genes were enriched in pathways related to adaptive immune response, cellular defense response and regulation of innate immune response. Conclusion: The tumor microenvironment plays a critical role in development of PTC and CXCL10 may serve as a novel target of precision therapy for this patient population.


Bioanalysis ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 461-470 ◽  
Author(s):  
Jian Chen ◽  
Hongwei Hou ◽  
Huan Chen ◽  
Yanbo Luo ◽  
Yunlu He ◽  
...  

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5110
Author(s):  
Jaehyung Kim ◽  
Soo Young Kim ◽  
Shi-Xun Ma ◽  
Seok-Mo Kim ◽  
Su-Jin Shin ◽  
...  

In most cases, papillary thyroid cancer (PTC) is highly curable and associated with an excellent prognosis. Yet, there are several clinicopathological features that lead to a poor prognosis, underscoring the need for a better genomic strategy to refine prognostication and patient management. We hypothesized that PPARγ targets could be potential markers for better diagnosis and prognosis due to the variants found in PPARG in three pairs of monozygotic twins with PTC. Here, we developed a 10-gene personalized prognostic index, designated PPARGi, based on gene expression of 10 PPARγ targets. Through scRNA-seq data analysis of PTC tissues derived from patients, we found that PPARGi genes were predominantly expressed in macrophages and epithelial cells. Machine learning algorithms showed a near-perfect performance of PPARGi in deciding the presence of the disease and in selecting a small subset of patients with poor disease-specific survival in TCGA-THCA and newly developed merged microarray data (MMD) consisting exclusively of thyroid cancers and normal tissues.


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