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.

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.

Mechanism of Anti-Hepatic Fibrosis of TGF-β1/Smad Signaling Pathway Affected by Chymase Inhibitors

2020 ◽  
Vol 10 (6) ◽  
pp. 782-788
Author(s):  
Xue-Ji Han ◽  
Ning Chen ◽  
Ming-Shi Yin
Keyword(s):  
Protein Expression ◽  
Mrna Expression ◽  
Hepatic Fibrosis ◽  
Expression Level ◽  
Mrna Expression Level ◽  
Model Group ◽  
Protein Expression Level ◽  
Smad Signaling Pathway ◽  
Chymase Inhibitor ◽  
Liver Tissues

Objective: This study aims to investigate the pathological mechanism of chymase inhibitors (Chy-I) on liver tissue in rats with hepatic fibrosis. Methods: Rats in the model group and chymase inhibitor group were established by using carbon tetrachloride. Rats in the chymase inhibitor group intragastrically received Chy-I (10 mg/kg/d) during the modeling. The pathological changes of rat liver tissues induced by chymase inhibitors were investigated, and the mRNA and protein expression of TGF-β1, Smad3 and Smad7 were observed in rat liver tissues. Results: When compared to the model group, The results presented that the liver tissue pathology of rats had been significantly improved in the Chy-I group. When compared to the normal group, the mRNA expression level and protein expression level of TGF-β1 and Smad3 in liver tissues had significantly increased, but the mRNA expression level and protein expression level of Smad7 significantly decreased (p < 0 05). When compared to the model group, the mRNA expression level and protein expression level of TGF-β1 and Smad3 was significantly downregulated, but the mRNA expression level and protein expression level of Smad7 was significantly upregulated in the Chy-I group. Conclusion:Chy-I plays an active role in blocking hepatic fibrosis in rats by affecting the TGF-β1/Smad signaling pathway in liver tissues through multiple sites.

scholarly journals SHMT2 expression as a diagnostic and prognostic marker for thyroid cancer

2021 ◽  
Author(s):  
Meihua Jin ◽  
Woo Kyung Lee ◽  
Mi-Hyeon You ◽  
Ahreum Jang ◽  
Sheue-yann Cheng ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Protein Expression ◽  
Mrna Expression ◽  
Clinical Outcomes ◽  
Prognostic Marker ◽  
Thyroid Tissue ◽  
The Cancer Genome Atlas ◽  
Thyroid Carcinomas ◽  
Messenger Ribonucleic Acid ◽  
Benign Nodules

Background: Catabolism of serine via serine hydroxymethyltransferase2 (SHMT2) through the mitochondrial one-carbon unit pathway is important in tumorigenesis. Therefore, SHMT2 may play a role in thyroid cancer. Methods: Thyroid tissue samples and The Cancer Genome Atlas (TCGA) database were used to evaluate SHMT2 expression in thyroid tissues and the association with clinical outcomes. Results: SHMT2 protein expression was evaluated in thyroid tissues consisting of 52 benign nodules, 129 papillary thyroid carcinomas (PTC) and matched normal samples, and 20 anaplastic thyroid carcinomas (ATC). ATCs presented the highest (95.0%) positivity of SMHT2 protein expression. PTCs showed the second highest (73.6%) positivity of SHMT2 expression, which was significantly higher than that of benign nodules (19.2%, P =0.016) and normal thyroid tissues (0%, P<0.001). Analysis of TCGA data showed that SHMT2 messenger ribonucleic acid (mRNA) expression was significantly higher in tumors than normal tissues (P<0.001). When we classified thyroid cancer into high and low groups according to SHMT2 mRNA expression levels, the thyroid differentiation score for the high SHMT2 group was significantly lower than that of the low SHMT2 group (P<0.001). There was also a significant correlation between SHMT2 mRNA expression and the stemness index (r=0.41, P<0.001). High SHMT2 group had more advanced TNM stages and shorter progression-free survival rates than low SHMT2 group (P<0.01 and P =0.007, respectively). Conclusion: SHMT2 expression is higher in thyroid cancers than normal or benign tissues and is associated with dedifferentiation and poor clinical outcomes. Thus, SHMT2 might be useful as a diagnostic and prognostic marker for thyroid cancer.

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 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.

Circulating Cytokeratin 19 Fragments in Patients with benign Nodules and Carcinomas of the Thyroid Gland

2008 ◽  
Vol 23 (1) ◽  
pp. 54-57 ◽  
Author(s):  
L. Giovanella ◽  
L. Ceriani ◽  
A. Ghelfo ◽  
M. Maffioli
Keyword(s):  
Thyroid Carcinoma ◽  
Thyroid Nodules ◽  
Differentiated Thyroid Carcinoma ◽  
Cytokeratin 19 ◽  
Thyroid Carcinomas ◽  
Poorly Differentiated ◽  
Benign Nodules ◽  
Thyroid Malignancies ◽  
Benign Thyroid Nodules ◽  
Benign Thyroid

Cytokeratin 19 (CK19) is an acidic protein of 40 kDa that is part of the cytoskeleton of epithelial cells and is highly expressed by differentiated thyroid carcinomas, mainly of the papillary subtype. The soluble fragments of CK19 (Cyfra 21.1) can be measured by immunometric assays employing specific monoclonal antibodies. The present study was planned to assess the serum expression of Cyfra 21.1 in patients with benign thyroid nodules and thyroid malignancies. We enrolled 135 patients with histologically proven benign thyroid nodules (n=79) and thyroid carcinomas (n=56). No differences were found in serum Cyfra 21.1 levels between patients with benign nodules and patients with carcinomas. When thyroid malignancies were subdivided according to tumor histology, serum Cyfra 21.1 increased significantly from classical differentiated thyroid carcinomas (papillary or follicular) to less differentiated or undifferentiated carcinomas (poorly differentiated or anaplastic). CK19 release into the bloodstream is strongly related to the apoptotic pathway, and particularly to hyperproliferation-related apoptosis. These pathways characterized anaplastic and poorly differentiated thyroid carcinoma but not classical forms of differentiated thyroid carcinoma. Consequently, Cyfra 21.1 may be regarded as a circulating marker of poorly differentiated and anaplastic thyroid carcinoma. Additionally, a role of Cyfra 21.1 as a dedifferentiation marker in patients with classical differentiated thyroid carcinomas may be postulated and should be explored by further focused studies.

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