Progression Of Thyroid Carcinoma Research Articles

Identifying gene modules of thyroid cancer associated with pathological stage by weighted gene co-expression network analysis

Thyroid cancer is the most common type of endocrine tumor. The TNM classification remains a standard for treatment determination and predicting prognosis in thyroid cancer. The genes modules associated with the progression of papillary thyroid carcinoma (PTC) were not clear. We applied a weighted gene co-expression network analysis (WGCNA) and differential expression analysis to systematically identified co-expressed gene modules and hub genes associated with PTC progression based on The Cancer Genome Atlas (TCGA) PTC transcriptome sequencing data. An independent validation cohort, GSE27155, was used to evaluate the preservation of gene modules. We identified two co-expressed genes modules associated with progression of PTC. Enrichment analysis indicated that the two modules were enriched in angiogenesis and extracellular matrix organization. DCN, COL1A1, COL1A2, COL5A2 and COL3A1 were hub genes in the co-expressed network. We systematically identified co-expressed gene modules and hub genes associated with PTC progression for the first time, which provided insights into the mechanisms underlying PTC progression and some potential targets for the treatment of PTC.

CircRNA circ_0067934 Overexpression Correlates with Poor Prognosis and Promotes Thyroid Carcinoma Progression.

BackgroundCircular RNAs are important regulators in human cancers, including thyroid carcinoma. The circ_0067934 RNA is reported to participate in hepatocellular carcinoma, esophageal squamous cell carcinoma, and lung cancer. Whether it regulates thyroid carcinoma remains unclear. The purpose of this study was to research potential mechanisms of circ_0067934 in thyroid tumors to provide potential new diagnostic and treatment targets.Material/MethodsThe expression level of circ_0067934 in thyroid tumors, adjacent tissues, and cell lines was measured by qRT-PCR. The Kaplan-Meier survival curve analysis was used to explore the relationship between circ_0067934 level and survival time of patients. Circ_0067934 was knocked down to research its functional role in thyroid tumors. Cell proliferation was detected by CCK-8 (cell counting kit-8) assay. Migration and invasion were analyzed by Transwell assay. Western blot was applied to analyze the expression of epithelial-mesenchymal-transition (EMT) and PI3K/AKT related proteins.ResultsCompared with adjacent tissue, circ_0067934 was highly expressed in thyroid tumors. Circ_0067934 expression level was highly expressed in thyroid tumor cell lines. Patients with high expression of circ_0067934 showed lower survival rates. Knockdown of circ_0067934 inhibited cell proliferation, migration, and invasion and also promoted apoptosis. In addition, circ_0067934 knockdown inhibited EMT and PI3K/AKT signaling pathways.Conclusionscirc_0067934 could improve the development of thyroid carcinoma by promoting EMT and PI3K/AKT signaling pathways.

SP1-induced upregulation of long noncoding RNA LINC00313 contributes to papillary thyroid cancer progression via the miR-422a.

Long noncoding RNA LINC00313 (LINC00313) has been reported to be dysregulated in several tumors, including papillary thyroid carcinoma (PTC). Our present study aimed to further explore the potential mechanism of LINC00313 in the progression of papillary thyroid carcinoma (PTC). RT-PCR was performed to detect the expression of LINC00313 in both PTC tissues and cell lines. Luciferase reporter and chromatin immunoprecipitation (ChIP) assays were performed to explore whether SP1 could bind to the promoter region of LINC00313 and activate its transcription. The biological functional correlation of LINC00313 was determined by down-regulating the expression of LINC00313 on PTC cell proliferation, apoptosis, migration and invasion. The regulating relationship between LINC00313 and miR-422a was investigated in PTC cells using luciferase reporter assays. We observed that LINC00313 expression was significantly up-regulated in both PTC tissues and cell lines. Next, the results of bioinformatics analysis and luciferase reporter assays indicated that the transcription factor SP1 can bind to the promoter region of LINC00313 resulting in the overexpression of LINC00313 in PTC. Moreover, functional study revealed that knockdown of LINC00313 significantly suppressed cells proliferation, migration, invasion and EMT. Finally, our results indicated that LINC00313 functioned as an oncogene in PTC in part through serving as a competing endogenous RNA to modulate mi-422a expression. Overall, our data demonstrated that SP1-induced LINC00313 contributed to PTC progression by via competitively binding to miR-422a, which may provide a novel therapeutic strategy for PTC.

Expression and clinicopathological role of miR146a in thyroid follicular carcinoma.

Dysregulation of microRNA expression has been involved in the development and progression of follicular thyroid carcinoma (FTC). The aim of this work was to study the expression of miRNA146a in FTC and the association with clinicopathological features of the disease. Thirty-eight patients affected by FTC were included in the study. Twenty patients carrying follicular thyroid adenoma (FA) were also enroled as the benign counterpart of FTC. Total RNA including miRNA146a was extracted from formalin-fixed paraffin-embedded (FFPE) pairs of affected/unaffected tissue and its expression was assessed by real-time PCR. Two selected target genes, TRAF6 (tumour necrosis factor receptor-associated factor 6) and IRAK1 (Il-1 receptor-associated kinase 1/2), were also analysed. miR146a expression in FTC tissue was overall not downregulated in malignant versus unaffected tissue, but its expression was inversely correlated with clinicopathological features of FTCs at diagnosis. A decreased expression of miR146a became apparent in FTC thyroid tissue of widely compared to minimally invasive tumours. However, miR146a expression differences between contralateral unaffected tissue (extra-FTC) and FTC were not observed regardless of clinicopathological features. IRAK1, a known target for miR146a, was upregulated in FTC and the increase was mainly appreciable in Hurtle FTC variant. Unexpectedly, miR146a did not correlate with TRAF6 showing an inverse trend compared to IRAK1 although both genes regulate the activity of nuclear factor- kB (NF-kB). The results of this study indicate that downregulation of miR146a, inversely correlated with clinicopathological features of FTCs at diagnosis and suggest a possible involvement of miR146a in FTC development. IRAK1 over-expression in FTC may be related to tumour development/progression. In vitro experiments are needed to support this hypothesis.

MiR‑584‑5p regulates migration and invasion in non‑small cell lung cancer cell lines through regulation of MMP‑14.

An increasing number of studies have demonstrated that microRNAs (miRNAs/miRs) are involved in cancer progression. In 2010, an estimated 1,500,000patients suffered mortality from lung cancer (LC) worldwide, and ~80% of LC patients were diagnosed with non‑small‑cell lung cancer(NSCLC). miR‑584‑5p was reported to be a potential biomarker in the diagnosis of LC; in addition, miR‑584 was recently observed to suppress the progression of thyroid carcinoma, glioma and gastric cancer. However, the specific function of miR‑584‑5p in NSCLC remains unclear. In the present study, miR‑584‑5p was decreased in the tumor tissues of NSCLC patients. Furthermore, miR‑584‑5p markedly inhibited the migration and invasion of NSCLC cells. The direct regulatory association between miR‑584‑5p and matrix metalloproteinase (MMP)‑14 was verified by a luciferase reporter gene assay. Furthermore, the results indicated that miR‑584‑5p inhibited the expression of MMP‑14 at the protein and mRNA levels. miR‑584‑5p also inhibited the expression of MMP‑4 and Slug, which are involved in tumor invasion and metastasis. Taken together, these results indicated that the miR‑584‑5p/MMP‑14 axis may serve as an anticancer target in the treatment of NSCLC patients.

The role of thyroid stimulating hormone level as a predictive factor for advance stage thyroid carcinoma

Thyroid stimulating hormone (TSH) is a cancer growth stimulus factor that have effect on the progression of thyroid carcinoma, common neck head malignancy. This hormonelevel has diagnostic value and can assist in the diagnosis, staging and management of the thyroid carcinoma.This study aimed to investigatethe role of TSH level as a predictor of advance stage thyroid carcinoma. This was case-control study involvingthyroid enlargement subjects who underwent thyroidectomy at Dr. Sardjito General Hospital, Yogyakartafrom 2015 to 2017. Cancer staging examination using AJCC 2102and TSH levels examination were conducted before underwent thyroidectomy.The inclusion criteria for case group were advanced stage(stage III and IV), while for control group wereearly-stage of thyroid carcinoma (stage I and II). The exclusion criteria for both case and control groups were 1) suffering from thyroid hormone disorders requiring therapy before thyroidectomy, 2) receiving thyroid suppression therapy prior to thyroidectomy. Sixty-six post thyroidectomy patients were involved in this study. The patients were divided into case and control groups consisted of 33 patients in each group. Based on receiver operating characteristic curve, the cut of point 1.27 mIU/L for TSH was obtained with sensitivity of 72.7% and specificity of 78.8%. There was statistically significant difference TSH levelsbetween early stage thyroid carcinoma and late stage thyroid carcinoma(p = 0.001;OR: 9.9;95% CI: 3.19-30.15).It can be concluded that TSHlevels ≥ 1.27mIU/L as predictor of advance stage thyroid carcinoma.

Knockdown of circPVT1 inhibits progression of papillary thyroid carcinoma by sponging miR-126.

Background: Papillary thyroid carcinoma (PTC) is the most common thyroid cancer. Recent studies have reported that circular RNAs (circRNAs) play essential roles in human cancers, including PTC. However, the roles of circRNA plasmacytoma variant translocation 1 (PVT1) in PTC progression and its potential mechanism remain largely unknown. Methods: The expressions of circPVT1 and microRNA-126 (miR-126) were measured in PTC tissues and cells by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability, apoptosis, migration and invasion were detected in PTC cells by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), flow cytometry, Western blot or trans-well assays, respectively. The interaction between circPVT1 and miR-126 was explored by bioinformatics analysis, luciferase activity assay and RNA immunoprecipitation. A mouse xenograft model was established to investigate the role of circPVT1 in PTC progression in vivo. Results: High expression of circPVT1 was shown in PTC tissues and cells and was associated with poor outcomes of patients. Knockdown of circPVT1 suppressed viability, migration and invasion but induced apoptosis in PTC cells. miR-126 was bound to circPVT1 and reduced in PTC tissues and cells. Moreover, inhibition of miR-126 reversed the regulatory effect of the circPVT1 interference on viability, apoptosis, migration and invasion in PTC cells. Besides, circPVT1 knockdown attenuated tumor growth via up-regulating miR-126 in vivo. Conclusion: CircPVT1 knockdown inhibited PTC progression by sponging miR-126. This may indicate circPVT1 as a novel target for treatment of PTC.

MicroRNA Expression in the Progression and Aggressiveness of Papillary Thyroid Carcinoma.

In the last two decades microRNAs have received great attention in research because of their ability to regulate gene expression. Many studies have shown that defects in different microRNA molecules are linked to many diseases; however, their contribution towards thyroid disease has not been fully explored. Herein, we present a short review of the present state of knowledge on microRNAs, such as their origin, their biogenesis and biological function, as well as their differential expression in papillary thyroid carcinoma. Dysregulated microRNA has been closely linked to thyroid dysfunction and oncogenicity leading to this type of thyroid cancer. The effects of Single Nucleotide Polymorphisms in microRNA are also discussed with respect to papillary thyroid carcinoma.

MiR-let-7e inhibits invasion and magration and regulates HMGB1 expression in papillary thyroid carcinoma

Thyroid cancer keeps rapidly increasing worldwide and the most frequent type is papillary thyroid carcinoma (PTC). MicroRNAs (miRNAs) are proved dysregulated in many types of malignancies, including thyroid cancer. Although miR-let-7e has been implicated in several types of cancer regulation, relatively little is known about the function of miR-let-7e in PTC. In this study, we showed that the overexpression of miR-let-7e or knockdown of high mobility group box 1 (HMGB1) inhibited cell migration and invasion. MiR-let-7e downregulates HMGB1 expression by directly targeting the HMGB1 3′-UTR. Furthermore, HMGB1 reintroduction reversed the anti-proliferation, anti-migration, and anti-invasion roles of miR-let-7e. miR-let-7e might function as a tumor suppressor in papillary thyroid carcinoma through HMGB1. Therefore, our study demonstrates that miR-let-7e plays an important role in papillary thyroid carcinoma progression and might represent a new potential therapeutic target for treatment.

MMP-9-1562 C/T single nucleotide polymorphism associates with increased MMP-9 level and activity during papillary thyroid carcinoma progression

Papillary thyroid carcinoma (PTC), a common form of thyroid malignancy, displays significant variations in clinical features and outcome. The malignant transformation of the thyroid is driven by altered expression of many matrix-modulating enzymes, including matrix metalloproteinase-9 (MMP-9). A single nucleotide polymorphism in its promotor (-1562 C/T) is suspected to cause overexpression of MMP-9, which in turn contributes to development of a tumour unfavourable phenotype. The aim of this study was to investigate the impact of MMP-9 promotor genotype on MMP-9 expression in PTC samples, and to assess its value as a possible risk factor for developing PTC or its aggressive phenotype. A total of 105 PTC patients and 43 healthy controls were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. In order to estimate MMP-9 expression, PTC tissue sections were stained immunohistochemically. Statistical analysis showed that PTC cases and controls did not differ significantly in genotype frequencies (OR= 2.27, CI= 0.854-6.022). In PTC samples, the presence of the T allele was accompanied by elevated MMP-9 expression (p= 0.047) as well as a higher risk of developing extrathyroid extensions (p= 0.037) and high TNM stages (p= 0.009). Moreover, we observed overexpression of MMP-9 in cases presenting with extrathyroid invasion (p= 0.001), lymph node metastasis (p= 0.028), large tumour size (p= 0.031) and advanced stage (p= 0.005) compared to indolent tumours, along with enhanced enzymatic activity demonstrated by in situ zymography. Data suggests that MMP-9 (-1562 C/T) does not facilitate predisposition for PTC but affects the disease course by modulating MMP-9 expression. Genotyping MMP-9 provides important information which may prove beneficial in risk stratification of PTC patients.

MiR-128 suppresses the growth of thyroid carcinoma by negatively regulating SPHK1

Accumulating evidences have emphasized the essential roles of differentially expressed miRNAs in papillary thyroid cancer (PTC) and follicular thyroid carcinoma (FTC) progression. MiR-128 has been reported to be down-regulated in multiple cancers to restrain tumor growth. However, the role of miR-128 in the development of PTC and FTC and the underlying mechanism remain to be unclear. In this present study, the results indicated that miR-128 expression was markedly down-regulated in PTC and FTC tissues and various thyroid carcinoma cell lines. Functional analysis indicated that over-expression of miR-128 suppressed PTC and FTC cancer cell growth, induced apoptosis and cell cycle arrest in G0/G1 phase. In addition, miR-128 over-expression markedly inhibited cancer cell migration and invasion. However, the processes above were reversed by silencing miR-128 expressions in thyroid tumor cells. Following, we characterized sphingosine kinase-1 (SPHK1) as a direct target of miR-128 that interacted with the 3′-untranslated region (UTR) of SPHK1, and the results were confirmed by using luciferase-reporter assay. We also observed that SPHK1 expression was decreased and negatively correlated with miR-128 expression in PTC and FTC tissues clinically. Importantly, ectopic expression of SPHK1 significantly abrogated the tumor-suppressive effect induced by miR-128, as supported by the reduced apoptosis, while the enhanced proliferation and metastasis. Finally, over-expressing miR-128 apparently reduced the tumor growth rate and tumor weight in vivo using xenograft tumor model, accompanied with a remarkable decrease of SPHK1. Thus, our study illustrated that miR-128 might be a tumor suppressor microRNA that played an essential role in thyroid carcinoma progression.

MiR-149-5p inhibits cell proliferation and invasion through targeting GIT1 in medullary thyroid carcinoma.

Previous studies indicate that miR-149 could both inhibit and promote the development of human cancer depending on the tumor type. GIT1 was found to play an important role in regulating cell migration. However, the specific function of miR-149-5p and GIT1 in the progression of medullary thyroid carcinoma (MTC) remains unknown. The purpose of this study was to confirm the function of miR-149-5p in MTC and explore its downstream regulation. Moreover, miR-149-5p level in MTC was detected via RT-quantitative PCR (RT-qPCR). GIT1 expression levels were assessed by RT-qPCR and western blot analysis. The cell proliferation and invasion were detected through MTT or Transwell assay respectively. In addition, miR-149-5p was identified to directly target GIT1 in MTC via dual luciferase assay. The results suggested that miR-149-5p level was obviously declined in MTC. Functionally, miR-149-5p overexpression inhibited proliferation and invasion. Moreover, miR-149-5p directly targeted GIT1 and was negatively associated with its expression in MTC. Conversely, GIT1 expression was obviously increased in MTC. GIT1 overexpression partially reversed the inhibitory action of miR-149-5p in MTC. miR-149-5p suppressed the proliferation and invasion of MTC cells through targeting GIT1, which would create new therapeutic avenues for MTC treatment.

BRAF V600E and RET/PTC Promote the Activity of Nuclear Factor-κB, Inflammatory Mediators, and Lymph Node Metastasis in Papillary Thyroid Carcinoma: A Study of 50 Patients in Inner Mongolia.

BackgroundThe aim of this study was to investigate the expression of the BRAF V600E gene mutation and the RET/PTC gene rearrangement in the progression of papillary thyroid carcinoma (PTC) in 50 patients from Inner Mongolia.Material/MethodsClinical data, blood, and tissue samples were obtained from 50 patients with PTC and ten patients with benign thyroid adenoma. Expression of BRAF V600E, RET/PTC, nuclear factor-κB (NF-κB), interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, C-X-C motif chemokine ligand (CXCL)1, CXCL2, C-C motif chemokine ligand (CCL)2, and CCL3 were measured using polymerase chain reaction (PCR), immunohistochemistry, and an enzyme-linked immunosorbent assay (ELISA).ResultsOf the 50 patients with PTC, 37 patients expressed the BRAF V600E gene mutation, eight patients expressed RET/PTC, and five patients showed concomitant BRAF V600E and RET/PTC. Time to recurrence for patients with PTC with BRAF V600E was significantly increased compared with patients with concomitant BRAF V600E mutation and RET/PTC rearrangement (P<0.05). Expression of BRAF V600E, RET/PTC, and concomitant expression of BRAF V600E and RET/PTC were significantly associated with patient age and lymph node metastasis (P<0.05). Serum levels of NF-κB, IL-1β, IL-6, TNF-α, TGF-β and CCL3, and tumor tissue levels of IL-1β, IL-6, TNF-α, TGF-β, CXCL2 and CCL2 in patients with PTC were significantly increased compared with patients with benign thyroid adenoma, before and after surgery (P<0.05).ConclusionsExpression of the BRAF V600E mutation and RET/PTC translocation promoted the activity of NF-κB, expression of inflammatory mediators, and lymph node metastases in patients with PTC.

Роль макрофагів у прогресуванні папілярного раку щитоподібної залози

Роль макрофагів у прогресуванні папілярного раку щитоподібної залози

PATHOLOGICAL PAIN: CAN IT BE SAFELY CURED?

The aim of this study was to evaluate the relation between the level of thyroid stimulating hormone (TSH) and progression of papillary thyroid carcinoma (PTC) with or without BRAFV600E mutation.The medical records and laboratory data of 547 patients with PTC and 94 patients with follicular adenoma (FA) were collected. The relationship between hormones levels and such end-points as extrathyroid extension (ETE), lymphovascular invasion (LVI) and lymph node metastasis (LNM) was assessed. In addition, age, gender, BRAFV600E mutation status, histological type and Hashimoto’s thyroiditis (HT) were considered.Most of the patients with PTC had hormones levels within the normal range, however, serum TSH concentration was significantly higher in PTC comparing with FA (P = 0.022). High levels of TSH in PTC were more frequent among women rather than men (P = 0.03) due to the gender differences in coexisting HT rate (P = 0.003). In contrast, LNM rate was higher in men (P = 0.0014). Coexisting HT significantly decreased the risk of ETE (OR = 0.67; 95%CI 0.44–1.00; P = 0.05) and LNM (OR = 0.59; 95%CI 0.37−0.94; P = 0.028) among males with PTC. However, there was no significant relationship between HT and PTC-related ETE and LNM in females. BRAFV600E mutation was associated with presence of lymphocytic infiltration (P < 0.001) but not with HT (P = 0.08) and violation of thyroid function.The present study showed the lack of significant relationship between TSH levels and PTC aggressiveness (LNM, TNM stage, BRAFV600E mutation). Higher TSH levels were found in patients with coexisting HT that was associated with female sex and multifocality of PTC.

Detection of Molecular Alterations in Taiwanese Patients with Medullary Thyroid Cancer Using Whole-Exome Sequencing.

Genetic and epigenetic alterations are associated with the progression and prognosis of medullary thyroid carcinoma (MTC). We performed whole-exome sequencing of tumor tissue from seven patients with sporadic MTC using an Illumina HiSeq 2000 sequencing system. We conducted Sanger sequencing to confirm the somatic mutations in both tumor and matched normal tissues. We applied Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis with the Database for Annotation, Visualization, and Integrated Discovery and STRING for pathway analysis. We detected new somatic mutations in the BICD2, DLG1, FSD2, IL17RD, KLHL25, PAPPA2, PRDM2, PSEN1, SCRN1, and TTC1 genes. We found a somatic mutation in the PDE4DIP gene that had previously been discovered mutated in other tumors but that had not been characterized in MTC. We investigated pathway deregulation in MTC. Data regarding 1152 MTCs were assembled from the Catalogue of Somatic Mutations in Cancer (COSMIC) and seven of our patients. Ontological analysis revealed that most of the variants aggregated in pathways that included the signaling pathways of thyroid cancer, central carbon metabolism, microRNAs in cancer, PI3K-Akt, ErbB, MAPK, mTOR, VEGF, and RAS. In conclusion, we conducted wide-ranging exome-wide analysis of the mutational spectrum of MTC in Taiwan's population and detected novel genes with potential associations with MTC tumorigenesis and irregularities in pathways that resulted in MTC pathogenesis.

Upregulated hsa_circ_0004458 Contributes to Progression of Papillary Thyroid Carcinoma by Inhibition of miR-885-5p and Activation of RAC1.

BackgroundCircular RNAs (circRNAs), a class of noncoding RNAs, may act as biomarkers and therapeutic targets of various cancers. However, the effects of hsa_circ_0004458 in papillary thyroid carcinoma (PTC) are still very much unclear. We aimed to demonstrate the potential roles of hsa_circ_0004458 in the progression of PTC.Material/MethodsIn our study, qRT-PCR assay was performed to assess hsa_circ_0004458, miR-885-5p and RAC1 expressions. Dual-luciferase reporter assay was used to detect the regulatory effects of hsa_circ_0004458 on miR-885-5p, and miR-885-5p on RAC1. MTT and flow cytometry assays were used to measure the cell proliferation, cycle, and apoptosis abilities. Tumor formation assay in nude mice was performed to measure the tumor growth in vivo.ResultsOur results indicated that hsa_circ_0004458 was upregulated in PTC tissues and cells, while silencing of hsa_circ_0004458 suppressed PTC cell proliferation and promoted PTC cell cycle arrest and apoptosis in vitro. Tumor formation assay in nude mice showed that knockdown of hsa_circ_0004458 by siRNAs inhibited the growth of PTC tumor in vivo. In addition, we found that miR-885-5p was a direct target of hsa_circ_0004458, and silencing of hsa_circ_0004458 inhibited PTC cell proliferation by miR-885-5p. We also demonstrated that RAC1 was a direct target of miR-885-5p and silencing of RAC1 suppressed PTC cell proliferation.ConclusionsWe found that hsa_circ_0004458 promoted the progression of PTC by inhibition of miR-885-5p and activation of RAC1, and hsa_circ_0004458 may serve as a potential therapeutic target and biomarker for PTC.

High expression and localization of β-catenin and epidermal growth factor receptor identify high risk papillary thyroid carcinoma patients

We have evaluated the clinical significance of deregulated expression of β-catenin and epidermal growth factor receptor (EGFR) during papillary thyroid carcinoma (PTC) progression. Immunohistochemical expression of β-catenin and EGFR was analyzed in 104 archival tissues of PTC and 19 matched lymph node metastases (LNMs). β-catenin (39/104, 37.5%) and EGFR (58/104, 55.7%) were co-expressed and co-localized in primary PTCs (p < .0001), which was confirmed by double immunofluorescent staining. The high expression of each molecule, as well as their high cytosolic co-expression, correlated with adverse clinicopathological features of the patients (p < .05). High expression of the proteins did not associate with the presence of BRAFV600E mutation (p > .05), tested by mutant allele-specific PCR amplification. Although nuclear localization of β-catenin was found in a subset of PTC patients (16/104, 15.4%), no β-catenin mutations were found in exon 3 of the CTNNB1 gene (screened by PCR in combination with denaturing gradient gel electrophoresis and confirmed by next generation sequencing). Cases with additional nuclear β-catenin staining showed strong association with high EGFR expression (15/16, 93.7%), the presence of capsule invasion (12/16, 81.25%) and regional LNM (9/16, 52.3%). In corresponding LNMs, β-catenin and EGFR expressions were maintained at high levels or further increased. Co-expression of high levels of β-catenin and EGFR in association with clinicopathological features implicates their clinical utility in risk stratification of PTC patients, and supports the possibility of crosstalk between Wnt/β-catenin and EGFR signaling during PTC progression.

Role of differentially expressed genes and long non-coding RNAs in papillary thyroid carcinoma diagnosis, progression, and prognosis.

Currently, the combination of ultrasonography and fine-needle aspiration biopsy (FNAB) can not discriminate between benign and malignant tumor of thyroid in some cases. The main issue in assessing the patients with thyroid nodules is to distinguish thyroid cancer from benign nodules, and reduce diagnostic surgery. To identify potential molecular biomarkers for patients with indeterminate FNAB, we explored the differentially expressed genes (DEGs) and differentially expressed long non-coding RNAs (DElncRNAs) in TCGA database between 318 papillary thyroid carcinoma (PTC) tissues and 35 normal thyroid gland tissues by DESeq R. Furthermore, DEGs were verified by gene expression profile GSE33630. Ten top DEGs and DElncRNAs were identified as candidate biomarkers for diagnosis and Lasso (Least Absolute Shrinkage and Selection Operator) logistic regression analysis were performed to improve the diagnostic accuracy of them. Besides, partial molecular biomarkers of top DEGs and DElncRNAs were closely related to the tumor stage (T), lymph node metastasis (N), metastasis (M) and pathological stage of PTC, which could reflect behavior of tumor progression. According to multivariate Cox analysis, the combination of two DEGs (METTL7B and KCTD16) and two DElncRNAs (LINC02454 and LINC02471) could predict the outcome in a more exact way. In conclusion, top DEGs and DElncRNAs could raise diagnosis of PTC in indeterminate FNAB specimens, and some could function as molecule biomarkers for tumor progression and prognosis.

MicroRNA-1266 suppresses papillary thyroid carcinoma cell metastasis and growth via targeting FGFR2.

To explore the effects of microRNA-1266 (miR-1266) on metastasis and growth in papillary thyroid carcinoma cells and to provide therapeutic targets for papillary thyroid carcinoma. By quantitative Real-time polymerase chain reaction (PCR), miR-1266 expression level in 38 pairs of papillary thyroid carcinoma tissues and three breast cancer-derived cell lines was examined. After transfection with miR-1266 mimics, the effects of miR-1266 over-expression on cell proliferation, invasion and migration were analyzed. Further, we employed several databases for the target gene prediction. Dual-luciferase activity assay was performed to verify whether FGFR2 was the direct target gene of miR-1266. Western blotting was conducted to detect protein levels. MiR-1266 was significantly downregulated in papillary thyroid carcinoma tissue samples and cell lines. Over-expression of miR-1266 in papillary thyroid carcinoma cells significantly attenuated the cell proliferation, invasion, and migration. Dual-luciferase report assay and Western blotting confirmed that FGFR2 was a target gene of miR-1266. Furthermore, up-regulation of FGFR2 partially reversed the suppressive effects of miR-1266 over-expression on cell growth and progression. miR-1266 could inhibit cell proliferation and progression of papillary thyroid carcinoma via targeting FGFR2. Our findings might provide a new target for the diagnosis and treatment of papillary thyroid carcinoma.