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 ◽  
...  

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.

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A856-A856
Author(s):  
Narudee Churdsuwanrak ◽  
Robert Niihara ◽  
Kristiana Rood ◽  
Celina Yamauchi ◽  
Kharl Wright ◽  
...  

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.


2008 ◽  
Vol 93 (4) ◽  
pp. 1195-1202 ◽  
Author(s):  
Stéphanie Durand ◽  
Carole Ferraro-Peyret ◽  
Samia Selmi-Ruby ◽  
Christian Paulin ◽  
Michelle El Atifi ◽  
...  

Abstract Context: Detection of thyroid cancer among benign nodules on fine-needle aspiration biopsies (FNAB), which presently relies on cytological examination, is expected to be improved by new diagnostic tests set up from genomic data. Objective: The aim of the study was to use a set of genes discriminating benign from malignant tumors, on the basis of their expression levels, to build tumor classifiers and evaluate their capacity to predict malignancy on FNAB. Design: We analyzed the level of expression of 200 potentially informative genes in 56 thyroid tissue samples (benign or malignant tumors and paired normal tissue) using nylon macroarrays. Gene expression data were subjected to a weighted voting algorithm to generate tumor classifiers. The performances of the classifiers were evaluated on a series of 26 sham FNAB, i.e. FNAB carried out on thyroid nodules after surgical resection. Results: A series of 19 genes with a similar expression in follicular adenomas and normal tissue and discriminating follicular adenomas+normal tissue from the following: 1) follicular thyroid carcinomas (FTCs), 2) papillary thyroid carcinomas (PTCs), or 3) both FTCs and PTCs. These were used to generate four classifiers, the FTCs, PTCs, common (FTC+PTCs), and global classifiers. In 23 of the 26 sham FNAB, the four classifiers yielded a diagnosis in agreement with the diagnosis of the pathologist used as reference; in the three other cases, the correct diagnosis was given by three of four classifiers. Conclusions: We developed a procedure of molecular diagnosis of benign vs. malignant tumors applicable to the material collected by FNAB. The molecular test complied with a preclinical validation stage; it must be now evaluated on ultrasound-guided FNAB in a large-scale prospective study.


2019 ◽  
Vol 105 (5) ◽  
pp. 1366-1374 ◽  
Author(s):  
Michael G White ◽  
Rashmi R Maheshwari ◽  
Scott J Anderson ◽  
Rolando Berlinguer-Palmini ◽  
Claire Jones ◽  
...  

Abstract Context Although diabetes affects 40% to 50% of adults with cystic fibrosis, remarkably little is known regarding the underlying mechanisms leading to impaired pancreatic β-cell insulin secretion. Efforts toward improving the functional β-cell deficit in cystic fibrosis-related diabetes (CFRD) have been hampered by an incomplete understanding of whether β-cell function is intrinsically regulated by cystic fibrosis transmembrane conductance regulator (CFTR). Definitively excluding meaningful CFTR expression in human β-cells in situ would contribute significantly to the understanding of CFRD pathogenesis. Objective To determine CFTR messenger ribonucleic acid (mRNA) and protein expression within β-cells in situ in the unmanipulated human pancreas of donors without any known pancreatic pathology. Design In situ hybridization for CFTR mRNA expression in parallel with insulin immunohistochemical staining and immunofluorescence co-localization of CFTR with insulin and the ductal marker, Keratin-7 (KRT7), were undertaken in pancreatic tissue blocks from 10 normal adult, nonobese deceased organ donors over a wide age range (23–71 years) with quantitative image analysis. Results CFTR mRNA was detectable in a mean 0.45% (range 0.17%–0.83%) of insulin-positive cells. CFTR protein expression was co-localized with KRT7. One hundred percent of insulin-positive cells were immunonegative for CFTR. Conclusions For the first time, in situ CFTR mRNA expression in the unmanipulated pancreas has been shown to be present in only a very small minority (&lt;1%) of normal adult β-cells. These data signal a need to move away from studying endocrine-intrinsic mechanisms and focus on elucidation of exocrine–endocrine interactions in human cystic fibrosis.


2010 ◽  
Vol 17 (1) ◽  
pp. F91-F104 ◽  
Author(s):  
Pierlorenzo Pallante ◽  
Rosa Visone ◽  
Carlo Maria Croce ◽  
Alfredo Fusco

Carcinoma of the thyroid gland is an uncommon cancer, but one of the most frequent malignancies of the endocrine system. Most thyroid cancers are derived from the follicular cells. Follicular carcinoma is considered more malignant than papillary thyroid carcinoma (PTC), and anaplastic thyroid cancer (ATC) is one of the most lethal human cancers. Even though several genetic lesions have been already described in human thyroid cancer, particularly in the papillary histotype, the mechanisms underlying the development of these neoplasias are still far from being completely elucidated. Some years ago, several studies were undertaken to analyze the expression of microRNAs (miRNAs or miRs) in thyroid carcinoma to evaluate a possible role of their deregulation in the process of carcinogenesis. These studies showed an aberrant microRNA expression profile that distinguishes unequivocally among PTC, ATC, and normal thyroid tissue. Here, other than summarizing the current findings on microRNA expression in human thyroid carcinomas, we discuss the mechanisms by which microRNA deregulation may play a role in thyroid carcinogenesis, and the possible use of microRNA knowledge in the diagnosis and therapy of thyroid neoplasms.


2021 ◽  
Vol 1 (1) ◽  
pp. 14-31
Author(s):  
Dilara Fatma Akin Bali

Introduction: It has been aimed to analyze the role of pathogenic effects of mutation and expression anomalies occurring on diaphanous-related formin 1 (DIAPH1), WASP actin nucleation-promoting factor (WASP), myosin heavy chain 9 (MYH9), actinin alpha 1 (ACNT1), filamin A (FLNA), and tubulin beta 1 class VI (TUBB1), which are known as fundamental cellular skeleton proteins, on the development and progression of cancer via bioinformatic tools. Methods: The genome sequence and expression profiles of 594 Colorectal Cancer (CRC) patients were obtained via bioinformatic tools, which provide data for The Cancer Genome Atlas. The mutation patterns of six genes were determined in detail, and for the prediction of pathogenic properties of identified changes for CRC, Polymorphism Phenotyping v2, Screening for Non-Acceptable Polymorphisms, and the Catalogue Of Somatic Mutations In Can- cer were utilized. Apart from the mutation profile, the effects of existing mutations on messenger ribonucleic acid (mRNA) expression and survival were also identified. Moreover, the Search Tool for the Retrieval of Interacting Genes/Proteins network analysis was realized to further comprehend the functional relations of proteins in cellu- lar processes. Results: There have been 142 distinct point mutations, gene amplification, and deep deletions identified on DIAPH1, WAS, MYH9, ACNT1, FLNA, and TUBB1 genes. ACTN1 and FLNA low mRNA expression levels for DIAPH1 increased, and the mRNA expression level was statistically significant (p<0.05). Prognosis-wise, the effect of mRNA expression on survival in the absence of disease was meaningful for FLNA (p=0.011). Discussion and Conclusion: Bioinformatic analysis data in DIAPH1, WASP, MYH9, ACNT1, FLNA, and TUBB1 genes, which are important in CRC pathogenesis revealed in this study, will be a guide for future laboratory studies.


2021 ◽  
Author(s):  
Wenbo Yang ◽  
Caipeng Qin ◽  
Yiqing Du ◽  
Songchen Han ◽  
Wenjun Bai ◽  
...  

Abstract Background The expression of Siglec-15, as a critical immune suppressor, in renal clear cell carcinoma (ccRCC) was few evaluated and remains unclear, especially in protein level. As previous studies reported, tumor fibrosis plays an essential role in assessing the prognosis of ccRCC, but the exact mechanism is not precise. This study evaluated the expression of Siglec-15, its role in prognosis, and the association with tumor fibrosis in ccRCC.Methods: Immunohistochemistry was used to analyze the Siglec-15 expression in one tissue microarray (cohort A, tumor: n=134, adjacent normal tissues: n=29). Subsequently, the mRNA expression of Siglec-15 and its clinical significance in ccRCC were analyzed using The Cancer Genome Atlas database (TCGA, cohort B, n = 534) and samples. Spearman correlation coefficients were calculated for correlation analysis of correlated expression genes of Siglec-15, and then functional annotation analysis was obtained with correlated expression genes. We detected the tumor fibrosis grade in cohort C (n=32) via second harmonic generation/two-photon excitation fluorescence. Results: Siglec-15 was overexpressed in tumor tissues compared with adjacent normal tissues in both cohort A (n=29, p<0.001) and cohort C (n=25, p<0.001). However, there was no significant difference in mRNA expression of Siglec-15 between tumor and adjacent normal tissues in cohort B (p>0.05). Moreover, over-expression of Siglec-15 is associated with higher Fuhrman grade in cohort A&C (n=166, p=0.001, OR=3.132, 1.563-6.275), cohort B (n=534, p=0.008, OR=1.606, 1.138-2.267). Univariate Kaplan-Meir survival analysis showed that patients with high Siglec-15 mRNA expression had shorter survival periods without significance in cohort B (p=0.073). Multivariate analysis employing the Siglec-15 regression model revealed that AJCC and Fuhrman grade was the only significant independent prognostic indicators. Besides, an inverse correlation was found between Siglec-15 protein expression and the tumor's fibrosis level (p = 0.02).Conclusions: Siglec-15 expression increases in ccRCC compared with adjacent normal tissues. Siglec-15 was frequently expressed and positively associated with pathology grade in ccRCC. This study indicated a significant role of Siglec-15 in the prognosis and immunotherapy target of ccRCC. This study also found an inverse correlation between Siglec-15 protein expression and the fibrosis level of the tumor.


2001 ◽  
Vol 86 (6) ◽  
pp. 2697-2700 ◽  
Author(s):  
Orsolya Dohán ◽  
Zubair Baloch ◽  
Zsuzsa Bánrévi ◽  
Virginia Livolsi ◽  
Nancy Carrasco

ABSTRACT Here we report the analysis of the Na+/I− symporter (NIS) protein expression in 57 thyroid cancer samples by immunohistochemistry with high-affinity anti-NIS Abs. As many as 70% of these samples exhibited increased NIS expression with respect to the normal surrounding thyroid tissue. Most significantly, NIS was located in these samples either in both the plasma membrane and intracellular compartments simultaneously, or exclusively in intracellular compartments. This suggests that NIS is clearly expressed or even overexpressed in most thyroid cancer cells, but malignant transformation in some of these cells interferes either with the proper targeting of NIS to the plasma membrane, or with the mechanisms that retain NIS in the plasma membrane after it has been targeted. The results further indicate that, in addition to indicating NIS expression in cases where it is absent (∼30%), improvements in 131I radioablation therapy might result from promoting targeting of NIS to the plasma membrane in the majority (∼70%) of thyroid cancers.


1998 ◽  
Vol 83 (7) ◽  
pp. 2493-2496 ◽  
Author(s):  
Franco Arturi ◽  
Diego Russo ◽  
Martin Schlumberger ◽  
Jean-Antoine du Villard ◽  
Bernard Caillou ◽  
...  

Expression of the Na+/I− symporter (NIS) gene was investigated by RT-PCR in a selected series of 26 primary thyroid carcinomas (19 papillary, 5 follicular, and 2 anaplastic). Fifteen follicular adenomas (11 “cold ” and 4 “hot” adenomas) were also studied. Five of 19 papillary thyroid cancer did not express NIS messenger ribonucleic acid (mRNA). In all but 1 follicular cancer, NIS transcript was fully detected. In anaplastic tissue, NIS mRNA was only barely detected in 1 case. All of the follicular thyroid adenomas except 1 expressed the NIS gene. In contrast, all tumors studied excluding the anaplastic histotype fully expressed thyroglobulin and thyroid peroxidase mRNA transcripts. In 2 patients, a lower expression (3- to 5-fold) of NIS mRNA was found in metastasis by dot blot analysis compared with those in both normal and primary neoplastic thyroid tissue. Four of 8 differentiated thyroid cancer patients selected for the presence of metastases with negative posttherapy 131I total body scan showed the lack of NIS gene expression in their primary cancer. This defect, at least in these cases, is a somatic and intrinsic lesion of the primary cancer cells and is not due to a dedifferentiation process in the metastatic tissue. The early detection of the loss of NIS gene expression in the primary cancer, therefore, may provide useful information for the management of differentiated thyroid cancer patients.


Nanomaterials ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 2370
Author(s):  
María García-Vence ◽  
María del Pilar Chantada-Vázquez ◽  
José Manuel Cameselle-Teijeiro ◽  
Susana B. Bravo ◽  
Cristina Núñez

A thyroid nodule is the most common presentation of thyroid cancer; thus, it is extremely important to differentiate benign from malignant nodules. Within malignant lesions, classification of a thyroid tumor is the primary step in the assessment of the prognosis and selection of treatment. Currently, fine-needle aspiration biopsy (FNAB) is the preoperative test most commonly used for the initial thyroid nodule diagnosis. However, due to some limitations of FNAB, different high-throughput “omics” approaches have emerged that could further support diagnosis based on histopathological patterns. In the present work, formalin-fixed paraffin-embedded (FFPE) tissue specimens from normal (non-neoplastic) thyroid (normal controls (NCs)), benign tumors (follicular thyroid adenomas (FTAs)), and some common types of well-differentiated thyroid carcinoma (follicular thyroid carcinomas (FTCs), conventional or classical papillary thyroid carcinomas (CV-PTCs), and the follicular variant of papillary thyroid carcinomas (FV-PTCs)) were analyzed. For the first time, FFPE thyroid samples were deparaffinized using an easy, fast, and non-toxic method. Protein extracts from thyroid tissue samples were analyzed using a nanoparticle-assisted proteomics approach combined with shotgun LC-MS/MS. The differentially regulated proteins found to be specific for the FTA, FTC, CV-PTC, and FV-PTC subtypes were analyzed with the bioinformatic tools STRING and PANTHER showing a profile of proteins implicated in the thyroid cancer metabolic reprogramming, cancer progression, and metastasis. These proteins represent a new source of potential molecular targets related to thyroid tumors.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Natassia Elena Bufalo ◽  
Karina Colombera Peres ◽  
Larissa Teodoro ◽  
Paulo Latufi-Filho ◽  
Icleia Siqueira Barreto ◽  
...  

Abstract Vascular endothelial growth factors (VEGFs) are a family of proteins involved in several elements that play an important role in the development of blood vessels. Besides acting in angiogenesis, VEGFA has important roles in chemotaxis, for macrophages and granulocytes, and vasodilation. VEGFA binds to VEGFR2, that acts on the MAPK and PI3K pathways, fundamental pathways for thyroid carcinogenesis. In order to assess the expression of VEGFA and VEGFR2, in different thyroid nodules, we used a Tissue MicroArray including 91 benign (74 females, 16 males, 49.84±12.65years old) and 125 malignant thyroid nodules (97 females, 28 males, 46.57±14.87 years old). Clinical and pathology data were obtained from 47 goiters; 43 follicular adenomas (FA) and a total of 104 papillary thyroid carcinomas (PTC), including 35 classic papillary thyroid carcinomas (CPTC), 30 follicular variant of PTC (FVPTC), 25 oxifilic variant of PTC (OVPTC), 14 tall cell papillary thyroid carcinomas (TCPTC); and 21 follicular thyroid carcinomas (FTC). All patients were managed according to a standard protocol based on current guidelines and followed-up for 116.9±70.8 months. VEGFA protein expression did not differentiate benign from malignant thyroid nodules. However, VEGFA was more frequently expressed in the less differentiated thyroid tissues. In fact, 95.8% of the FTC had positive expression. On the contrary, the intensity of this protein expression was progressively lower according to the process of cellular dedifferentiation (Goiter: 21.4%; FA: 16.3%; PTC: 8.7% and FTC: 0.0%; x2 = 0.031). There was no difference in VEGFR2 expression between malignant and benign nodules (x2= 0.108), but this protein showed more intense expression in tissues that also presented Hürthle cells (x2 &lt;0.0001). We were not able to find any correlation, neither of VEGFA nor with VEGFR2 expression, and any other feature of aggressiveness, including invasion, metastasis, lymph node metastasis, and distant metastasis. We conclude that VEGFA and VEGFR2 expression may help identify less differentiated tumors and the analysis of a larger cohort may prove the clinical utility of these markers.


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