Evaluation of insulin-like growth factor II, cyclooxygenase-2, ets-1 and thyroid-specific thyroglobulin mRNA expression in benign and malignant thyroid tumours

2005 ◽  
Vol 152 (5) ◽  
pp. 785-790 ◽  
Author(s):  
D Fuhrer ◽  
M Eszlinger ◽  
S Karger ◽  
K Krause ◽  
C Engelhardt ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Mrna Expression ◽  
Differentiated Thyroid Cancer ◽  
Thyroid Nodules ◽  
Normal Thyroid ◽  
Factor Ii ◽  
Cox 2 ◽  
Benign Thyroid Nodules ◽  
Benign Thyroid ◽  
Mrna Expression Levels

Objective: We evaluated three markers (insulin-like growth factor II (IGF-II), cyclooxygenase-2 (COX-2) and ets-1) of thyroid growth stimulation and cell transformation together with a thyroid-specific marker (thyroglobulin (Tg)) for their potential to differentiate benign and malignant follicular thyroid neoplasia (FN). Design and methods: mRNA expression levels were determined by real-time PCR in 100 snap-frozen thyroid samples: 36 benign thyroid nodules with different histology and function (19 cold (CTN) and 17 toxic thyroid nodules (TTN)), 36 corresponding normal thyroid tissues of the same patients, eight Graves’ disease (GD) thyroids, 10 follicular thyroid carcinomas (FTC) and 10 papillary thyroid carcinomas (PTC). Results: Mean IGF-II and COX-2 levels were not significantly altered between benign and malignant thyroid nodules (IGF-II) or nodular (FTC, TTN, CTN) and normal thyroid tissues (COX-2). In contrast, eight- to tenfold upregulation of ets-1 was observed in PTC and three- to fourfold upregulation of ets-1 was observed in FTC (and GD) compared with benign thyroid nodules and normal thyroid tissues. In addition, thyroglobulin mRNA expression was markedly downregulated (50- to 100-fold) in FTC, PTC and GD samples compared with benign nodular and normal thyroid tissues. Hence an ets-1/Tg ratio >20 distinguished differentiated thyroid cancer from benign nodular or normal thyroid tissue. We then studied ets1- and Tg mRNA expression levels in fine needle aspiration cytology (FNAC) samples. However, in a consecutive series of 40 FNAC samples only equivocal results were obtained on 38 benign and two malignant (FTC) thyroid tumour samples. Conclusions: Upregulation of ets-1 and downregulation of Tg mRNA expression occur in differentiated thyroid cancer and may facilitate pre-operative identification of thyroid malignancy depending on further evaluation of these potentially promising markers in a larger series of benign and malignant thyroid tumours and their FNAC samples.

scholarly journals Homa-Ir Insulin Resistance in Differentiated Thyroid Cancer and Benign Thyroid Nodules

2021 ◽  
Author(s):  
Eloisa Castillo-Saavedra ◽  
Juan José Castillo-Dávila ◽  
Dania Lizet Quintanilla-Flores ◽  
Anally Jamile Soto-García
Keyword(s):  
Insulin Resistance ◽  
Thyroid Cancer ◽  
Thyroid Nodule ◽  
Differentiated Thyroid Cancer ◽  
Thyroid Nodules ◽  
Categorical Variables ◽  
Continuous Variables ◽  
Benign Thyroid Nodule ◽  
Benign Thyroid Nodules ◽  
Benign Thyroid

Abstract Introduction: There is evidence that insulin resistance is associated with different types of cancer. This resistance increases the incidence of benign thyroid nodules and the risk of developing Differentiated Thyroid Cancer, however, studies in this regard are required. Objective: To assess if there are differences in the prevalence of insulin resistance in patients with differentiated thyroid cancer and patients with benign thyroid nodule. Material and methods: Prospective, analytical and cross-sectional design study. Patients undergoing thyroidectomy and definitive diagnosis of differentiated thyroid cancer or benign thyroid nodule were included. Anthropometric and biochemical variables were evaluated and differences in prevalence of insulin resistance were identified. To compare continuous variables, Student's T or Mann Whitney's U was used. To evaluate differences in categorical variables, the two-sided Fisher test when two binary variables were contrasted and Pearson's X2 in variables with more than two categories. Factors were analyzed through multivariate analysis obtaining odds ratio and 95% confidence interval.Results: A lower possibility of cancer was concluded: hereditary-family history of thyroid disease and hypothyroidism (OR 0.159; 95% CI 0.038-0.669; p = 0.012). Positive HOMA-IR showed a significant association in residual structural disease (P = 0.050) and local vascular invasion (p = 0.014).Conclusions: No significant association was obtained between positive HOMA-IR and Differentiated Thyroid Cancer, compared with the Benignity group. It seems that there is a greater tendency to lack of structural and biochemical resolution in patients with malignancy and positive HOMA-IR.

scholarly journals Analysis of Enigma Gene-Signaling Pathways in Thyroid Cancer

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A856-A856
Author(s):  
Narudee Churdsuwanrak ◽  
Robert Niihara ◽  
Kristiana Rood ◽  
Celina Yamauchi ◽  
Kharl Wright ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Protein Expression ◽  
Mrna Expression ◽  
Thyroid Nodules ◽  
Expression Level ◽  
Mrna Expression Level ◽  
Indeterminate Nodules ◽  
Benign Nodules ◽  
Benign Thyroid Nodules ◽  
Benign Thyroid

Abstract Fine-needle aspiration (FNA) is one of the most accurate modes of obtaining thyroid nodule biopsies, however, up to 25% of biopsies still yield indeterminate results. There is an increasing number of thyroidectomies due to indeterminate nodules by FNA alone. Therefore, more accurate and time efficient diagnostic approaches for analyzing indeterminate thyroid nodules is required. Recent studies showed that Enigma is associated with different cancer types, including thyroid cancer progression and calcification through its interaction with bone morphogenic protein-1 (BMP-1) and tyrosine kinases linked to mitogen-activated protein kinase (MAPK) signaling pathway. Our published data on Enigma protein analysis with immunohistochemistry showed promising findings to discriminate malignant versus benign nodules. We also showed a thyroid cancer stage-dependent enhancement of Enigma protein expression. In this study, we are investigating Enigma at a gene expression level by quantitative reverse transcription polymerase chain reaction (RT-qPCR), which is more time-efficient, quantitative, and requires less tissue than immunohistochemistry. We extracted mRNA/DNA/proteins from fresh malignant and benign thyroid nodules using a Qiagen AllPrep DNA/RNA/Protein Mini Kit. After verification of the quantity and purity by NanoDrop, isolated mRNA was then run through Enigma-RT-qPCR. MAPK assay was done by western blotting using MAPK-antibody. Our initial results found that Enigma-mRNA expression level was 3-fold higher in malignant compared to benign thyroid tissues. This finding supports our previous protein expression data with a relative quantitative difference in Enigma-mRNA expression level between malignant and benign thyroid nodules. MAPK expression was upregulated in thyroid cancer compared to benign nodules. We conclude that Enigma-RT-qPCR can be used effectively in FNA samples derived from thyroid nodules, which could potentially enhance the diagnostic accuracy of indeterminate nodules and decrease unnecessary thyroidectomies. Furthermore, both Enigma and MAPK were highly expressed in advanced tumor in the same tissues. Future study is needed to establish the functional interaction of Enigma-MAPK activity in thyroid cancer cells.

scholarly journals MON-516 Quantitative Analysis of Differential Enigma/PDLIM7 Gene Expression in Thyroid Cancer vs. Benign Nodules

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Kari Roberts ◽  
Sang Hee K Choi ◽  
Ethan Frank ◽  
David Foulad ◽  
Saeid Mirshahidi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Thyroid Cancer ◽  
Mrna Expression ◽  
Cancer Progression ◽  
Thyroid Nodules ◽  
Quantitative Difference ◽  
Expression Level ◽  
Published Data ◽  
Benign Thyroid Nodules ◽  
Benign Thyroid

Abstract Thyroid cancer incidence is rising worldwide. Although fine-needle aspiration biopsy (FNAB) is an accurate modality for evaluating thyroid nodules, up to 25% of FNABs still yield indeterminate results. There is a considerable number of diagnostic thyroidectomies for benign disease as a result of indeterminate FNAB. A more accurate and time-efficient diagnostic approach for analyzing indeterminate thyroid nodules may reduce diagnostic thyroidectomy. Recently, the osteogenic protein, Enigma, has been associated with different cancer types, including thyroid cancer progression and calcification through its interaction with bone morphogenic protein-1 (BMP-1), and tyrosine kinases linked to mitogenic signaling pathways [1, 2]. Our published data on Enigma protein analysis with immunohistochemistry showed promising results in discriminating between malignant versus benign thyroid nodules and demonstrated a correlation with thyroid cancer staging [3]. In this study, we are investigating Enigma at a gene expression level by real-time (RT-qPCR), which is a quantitative and more time-efficient method that requires smaller samples (FNA) than immunohistochemistry. We analyzed Enigma mRNA expression levels to determine if Enigma-qPCR could be used as a diagnostic tool to improve the accuracy of FNAB in both malignant and benign thyroid tissues. We extracted mRNA/DNA/proteins from fresh malignant and benign thyroid nodules using a QIAGEN DNA/RNA/Protein Kit. We ran isolated pure mRNA through Enigma-qPCR. The results showed that the Enigma-mRNA expression was 3-fold higher in malignant as compared to benign thyroid tissues. This finding supports our previous Enigma immunohistochemistry data and shows a relative quantitative difference in Enigma-mRNA expression level between malignant and benign thyroid nodules. We conclude that Enigma-RT-qPCR can be used to effectively determine malignancies in FNAB samples derived from thyroid nodules. This method could potentially enhance the diagnostic accuracy of indeterminate nodules and decrease diagnostic thyroidectomies and associated morbidity. [1] C.R. Jung, J.H. Lim, Y. Choi, D.G. Kim, K.J. Kang, S.M. Noh, D.S. Im, Enigma negatively regulates p53 through MDM2 and promotes tumor cell survival in mice, The Journal of clinical investigation 120(12) (2010) 4493-506. [2] Y.J. Kim, H.J. Hwang, J.G. Kang, C.S. Kim, S.H. Ihm, M.G. Choi, S.J. Lee, Enigma Plays Roles in Survival of Thyroid Carcinoma Cells through PI3K/AKT Signaling and Survivin, Anticancer research 38(6) (2018) 3515-3525. [3] A.A. Firek, M.C. Perez, A. Gonda, L. Lei, I. Munir, A.A. Simental, F.E. Carr, B.J. Becerra, M. De Leon, S. Khan, Pathologic significance of a novel oncoprotein in thyroid cancer progression, Head & neck 39(12) (2017) 2459-2469.

scholarly journals Altered Serum MicroRNA Profile May Serve as an Auxiliary Tool for Discriminating Aggressive Thyroid Carcinoma from Nonaggressive Thyroid Cancer and Benign Thyroid Nodules

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Aisen Zhang ◽  
Cheng Wang ◽  
Hui Lu ◽  
Xi Chen ◽  
Yi Ba ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Thyroid Nodules ◽  
Serum Levels ◽  
Mirna Expression Profile ◽  
Control Group ◽  
Healthy Controls ◽  
Benign Nodule ◽  
Benign Thyroid Nodules ◽  
Benign Thyroid

Thyroid cancers are the most common malignancy of the endocrine system; however, there is no reliable blood biomarkers for thyroid cancer diagnosis and even for aggressive and nonaggressive thyroid cancers as well as benign nodule discrimination. The present study is aimed at evaluating whether circulating microRNA (miRNA) can differentiate aggressive and nonaggressive thyroid cancer from benign thyroid nodules. In this study, we performed a multiphase, case-control study to screen serum miRNA expression profile in 100 patients with papillary thyroid cancer (PTC), 15 patients with aggressive medullary thyroid carcinoma (MTC), 91 patients with benign nodules, and 89 healthy controls using TaqMan low-density array followed by extensive reverse transcription quantitative real-time PCR validation. The results showed that the serum levels of miR-222-3p, miR-17-5p, and miR-451a were markedly increased, while miR-146a-5p, miR-132-3p, and miR-183-3p were significantly decreased in the PTC and benign nodule groups compared with the control group. There was no difference in the miRNA expression profile between the PTC group and the benign nodule group. Nevertheless, the serum levels of miR-222-3p and miR-17-5p were significantly increased in the MTC group than the benign nodule and control group. Moreover, receiver operating characteristic curve analyses demonstrated that the 2 miRNAs and their panel can accurately discriminate MTC from the benign nodule group and healthy controls. These findings indicated that the altered circulating miRNAs may discriminate PTC and benign thyroid nodules from controls, and serum miR-222-3p and miR-17-5p have the potential to serve as auxiliary tools for diagnosing more aggressive thyroid carcinomas, such as MTC.

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