The Role of the NIS (SLC5A5) Gene in Papillary Thyroid Cancer: A Systematic Review.
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ABSTRACT:
SUBMITTER: de Morais RM
PROVIDER: S-EPMC6282135 | biostudies-literature | 2018
REPOSITORIES: biostudies-literature
Publications
The Role of the NIS (SLC5A5) Gene in Papillary Thyroid Cancer: A Systematic Review.
de Morais Rafael Martins RM Sobrinho Alaor Barra AB de Souza Silva Calliandra Maria CM de Oliveira Jamila Reis JR da Silva Izabel Cristina Rodrigues ICR de Toledo Nóbrega Otávio O
International journal of endocrinology 20181114
Papillary thyroid cancer (PTC) is the most common thyroid malignancy. Genetic and epigenetic alterations play a decisive role in the onset of several human neoplasms. Mutations and polymorphisms are two frequent genetic alterations. Located on chromosome 19 (19p13.11), the NIS SLC5A5 (solute carrier family 5 member 5) gene encodes a highly specialized and efficient 80-90 kDa transmembrane glycoprotein that mediates active transport of iodide from the bloodstream into the follicular cells. Given ...[more]
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Project description:NIS is a potent iodide transporter encoded by the SLC5A5 gene. Its expression is reduced in papillary thyroid carcinoma (PTC). In this study we analyzed the impact of miR-181a-5p on NIS expression in the context of PTC. We used real-time PCR to analyze the expression of SLC5A5 and miR-181a-5p in 49 PTC/normal tissue pairs. Luciferase assays and mutagenesis were performed to confirm direct binding of miR-181a-5p to the 3'UTR of SLC5A5 and identify the binding site. The impact of modulation of miR-181a-5p using appropriate plasmids on endogenous NIS and radioactive iodine accumulation was verified. We confirmed downregulation of SLC5A5 and concomitant upregulation of miR-181a-5p in PTC. Broadly used algorithms did not predict the binding site of miR-181a-5p in 3'UTR of SLC5A5, but we identified and confirmed the binding site through mutagenesis using luciferase assays. In MCF7 and HEK293-flhNIS cell lines, transfection with mir-181a-expressing plasmid decreased endogenous SLC5A5, whereas silencing of miR-181a-5p increased it. We observed similar tendencies in protein expression and radioactive iodine accumulation. This study shows for the first time that miR-181a-5p directly regulates SLC5A5 expression in the context of PTC and may decrease efficacy of radioiodine treatment. Accordingly, miR-181a-5p may serve as an emerging target to enhance the efficacy of radioactive iodine therapy.
| S-EPMC8200107 | biostudies-literature
Project description:ObjectivePapillary thyroid cancer (PTC) is the most common endocrine malignancy with a steadily increasing incidence. Researches have reported that tumor multifocality occurs in an extensive number of cases. Nevertheless, the clinical characteristics and prognostic value remained controversial. This study was performed to investigate the relationship between multifocal PTC and adverse clinicopathologic features and the prognosis.MethodsA systematic review and meta-analysis were conducted based on three electronic databases up to December 31, 2021. Parameters of interest included five clinical features (extrathyroidal extension, lymphovascular invasion, central lymph node metastasis, lateral lymph node metastasis, distant metastasis) and were pooled into risk ratios (RRs). Time-to-event data (recurrence-free survival and all-cause mortality) were evaluated using hazard ratios (HRs). Publication bias was examined using funnel plots and Egger's test.ResultsA total of 23 articles were included according to the inclusion criteria; all of the studies were retrospective cohorts. In comparison with unifocality, multifocality showed an increased risk of extrathyroidal extension (RR 1.38, 95% CI 1.25-1.53), lymphovascular invasion (RR 1.27, 95% CI 1.04-1.55), central lymph node metastasis (RR 1.21, 95% CI 1.12-1.30), lateral lymph node metastasis (RR 1.86, 95% CI 1.62-2.14), and distant metastasis (RR 1.35, 95% CI 1.03-1.76). Multifocal patients were predisposed to postoperative recurrence (HR 1.76, 95% CI 1.50-2.07). The rate of all-cause mortality did not reach a statistical difference.Level of evidence2.ConclusionMultifocal PTC is more aggressive in contrast to unifocal PTC and is accompanied by an increased risk of recurrence. They were usually diagnosed in higher grades and stages. To achieve the maximal benefit, we recommend personalized therapy and close follow-up for multifocal PTC patients. Further prospective studies will clarify the best-fitted treatment plans.
| S-EPMC9392403 | biostudies-literature
Project description:BackgroundBlack thyroid is a rare incidental finding during surgery. We report the case of a patient with papillary thyroid cancer who was incidentally found to have minocycline-induced black thyroid.Case descriptionA 29-year-old woman presented with a left thyroid nodule and metastatic papillary thyroid cancer involving the left neck level IV lymph nodes. She had a medical history of anxiety disorder with depression, severe acne, and rosacea, and had been taking benzodiazepines, selective serotonin reuptake inhibitors, isotretinoin, and minocycline for a few years. The patient underwent a total thyroidectomy with left central compartment neck dissection and ipsilateral modified radical neck dissection. A black thyroid gland was identified during thyroidectomy. During level IV dissection, we noticed a similar black discoloration in the adipose tissue of the lower neck. Pathological examination revealed brown pigmentation with few macrophages on several foci of the thyroid parenchyma. Brown pigmentation was not identified in the thyroid tumor, metastatic and normal lymph nodes, or background adipose tissue.ConclusionsWe report a case of papillary thyroid microcarcinoma with cervical lymph node metastases in a black thyroid. The clinical findings were consistent with those of previous reports. Based on the literature, it remains unclear if this minocycline triggered finding is associated with an increased frequency and/or aggressiveness of thyroid carcinomas. In the absence of adequate evidence, prolonged minocycline users should ideally undergo routine thyroid assessment to identify possible malignancy.
| S-EPMC10005984 | biostudies-literature
Project description:Label-free proteomics profiling of 37 paired tumor-normal tissues of papillary thyroid cancer
2024-02-08 | PXD044900 | Pride
Project description:The incidence of thyroid cancer has been on the increase in a number of countries, and certain genetic factors associated with the increased incidence of the papillary thyroid cancer (PTC) have been identified. However, little is known about the effect of mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, expressed in the thyroid. We hypothesized and investigated that CFTR single nucleotide polymorphisms (SNPs) may be associated with the risk and/or progression of PTC. A total of 105 PTC patients, confirmed by pathological tests, and 323 controls, without any thyroidal disease, were recruited. One promoter SNP (rs4148682) and one coding SNP (rs213950, Val470Met) in the CFTR gene were analyzed, using direct sequencing. The PTC patients were sub-grouped and compared by their clinical and pathological characteristics of PTC. The results showed that the association between SNPs in the CFTR gene and the development of PTC was statistically insignificant. However, in the clinical and pathological features, rs4148682 was found to be correlated with multifocal tumors, location and cervical node metastasis of PTC. rs231950 was also correlated with multifocal tumors, location and nodal metastasis of PTC. The G allele of rs213950 was correlated with increased risk of multifocal tumors and bilateral lobe location. However, in cervical lymph node metastasis, the A allele of rs213950 was found to reflect high risk. Our study suggests that the CFTR gene polymorphisms studied may not be associated with the development of PTC, but that rs4148682 and rs213950 may be associated with clinical features and prognosis, such as multifocality, location of cancer and cervical lymph node metastasis of PTC.
| S-EPMC3362433 | biostudies-literature
Project description:PurposeFollowing the nuclear accidents in Chernobyl and later in Fukushima, the nuclear community has been faced with important issues concerning how to search for and diagnose biological consequences of low-dose internal radiation contamination. Although after the Chernobyl accident an increase in childhood papillary thyroid cancer (PTC) was observed, it is still not clear whether the molecular biology of PTCs associated with low-dose radiation exposure differs from that of sporadic PTC.MethodsWe investigated tissue samples from 65 children/young adults with PTC using DNA microarray (Affymetrix, Human Genome U133 2.0 Plus) with the aim of identifying molecular differences between radiation-induced (exposed to Chernobyl radiation, ECR) and sporadic PTC. All participants were resident in the same region so that confounding factors related to genetics or environment were minimized.ResultsThere were small but significant differences in the gene expression profiles between ECR and non-ECR PTC (global test, p < 0.01), with 300 differently expressed probe sets (p < 0.001) corresponding to 239 genes. Multifactorial analysis of variance showed that besides radiation exposure history, the BRAF mutation exhibited independent effects on the PTC expression profile; the histological subset and patient age at diagnosis had negligible effects. Ten genes (PPME1, HDAC11, SOCS7, CIC, THRA, ERBB2, PPP1R9A, HDGF, RAD51AP1, and CDK1) from the 19 investigated with quantitative RT-PCR were confirmed as being associated with radiation exposure in an independent, validation set of samples.ConclusionSignificant, but subtle, differences in gene expression in the post-Chernobyl PTC are associated with previous low-dose radiation exposure.
| S-EPMC4869750 | biostudies-literature
Project description:BackgruoundThis study aims to elucidate the associations among dietary seaweed (gim and miyeok/dashima) and iodine intakes, the rs77277498 polymorphism of the SLC5A5 gene codifying the sodium/iodine symporter, and thyroid cancer risk in a Korean population.MethodsWe conducted a case-control study of 117 thyroid cancer cases and 173 controls who participated in the Cancer Screenee Cohort between 2002 and 2014 at the National Cancer Center, Korea. The amount of seaweed and iodine consumption (g/day) was estimated using the residual energy adjustment method. We calculated odds ratios (ORs) and their 95% confidence intervals (CIs) using a multivariable logistic regression model for the separate and combined effect of dietary iodine-based intake and SLC5A5 polymorphism (rs77277498, C>G) on thyroid cancer.ResultsDietary gim and iodine intakes were inversely associated with thyroid cancer, with ORs of 0.50 (95% CI, 0.30 to 0.83) and 0.57 (95% CI, 0.35 to 0.95), respectively, whereas the associations for dietary miyeok/dashima and total seaweed intakes were not significant. However, compared with individuals carrying the C/C genotype of the rs77277498 polymorphism with a low intake of all dietary factors, those carrying the G allele with a high intake had a lower risk of thyroid cancer, with ORs of 0.25 (95% CI, 0.10 to 0.56), 0.31 (95% CI, 0.12 to 0.77), 0.26 (95% CI, 0.10 to 0.62), and 0.30 (95% CI, 0.12 to 0.73) for the consumption of gim, miyeok/dashima, total seaweed, and iodine, respectively.ConclusionIn summary, our results supported the evidence of the protective effects of dietary gim and iodine intake against thyroid cancer risk, and this association can be strengthened by SLC5A5 rs77277498 genotypes.
| S-EPMC9262681 | biostudies-literature
Project description:Papillary carcinomas account for the largest proportion of thyroid cancers, with papillary thyroid carcinoma (PTC) being prone to early lymph node metastasis. Some studies have confirmed that LPAR5 can promote the progression of PTC, but immune-related analyses of LPAR5 and PTC have not been widely discussed. This study aimed to determine the role of LPAR5 in PTC prognosis and immunity. We will further explore the role of LPAR5 in 33 different tumor types. Regarding PTC, we analyzed the effect of LPAR5 expression on overall survival (OS). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. Immune-related analyses of immune checkpoints (ICPs) and immune cell infiltration were also performed. For pan-cancer, R packages were used to analyze prognosis, tumor mutational burden (TMB), microsatellite instability (MSI), and immune cell infiltration. Analysis of tumor microenvironment (TME) and ICPs was performed using Sangerbox ( http://vip.sangerbox.com/home.html ). The TISIDB database ( http://cis.hku.hk/TISIDB/index.php ) was used to identify immune and molecular subtypes. LPAR5 expression is associated with PTC prognosis and immunity as well as various human tumors. LPAR5 may be a potential biomarker for multiple malignancies and may provide a new target for cancer immunotherapy.
| S-EPMC10086052 | biostudies-literature
Project description:The mammalian target of rapamycin (mTOR) pathway is overactivated in thyroid cancer (TC). We previously demonstrated that phospho-mTOR expression is associated with tumor aggressiveness, therapy resistance, and lower mRNA expression of SLC5A5 in papillary thyroid carcinoma (PTC), while phospho-S6 (mTORC1 effector) expression was associated with less aggressive clinicopathological features. The distinct behavior of the two markers led us to hypothesize that mTOR activation may be contributing to a preferential activation of the mTORC2 complex. To approach this question, we performed immunohistochemistry for phospho-AKT Ser473 (mTORC2 effector) in a series of 182 PTCs previously characterized for phospho-mTOR and phospho-S6 expression. We evaluated the impact of each mTOR complex on SLC5A5 mRNA expression by treating cell lines with RAD001 (mTORC1 blocker) and Torin2 (mTORC1 and mTORC2 blocker). Phospho-AKT Ser473 expression was positively correlated with phospho-mTOR expression. Nuclear expression of phospho-AKT Ser473 was significantly associated with the presence of distant metastases. Treatment of cell lines with RAD001 did not increase SLC5A5 mRNA levels, whereas Torin2 caused a ~6 fold increase in SLC5A5 mRNA expression in the TPC1 cell line. In PTC, phospho-mTOR activation may lead to the activation of the mTORC2 complex. Its downstream effector, phospho-AKT Ser473, may be implicated in distant metastization, therapy resistance, and downregulation of SLC5A5 mRNA expression.
| S-EPMC5983778 | biostudies-literature
Project description:ObjectiveThe hobnail variant of papillary thyroid carcinoma (HVPTC) has emerged as a rare and aggressive variant of papillary thyroid carcinoma (PTC). We aim to determine the prevalence and clinicopathologic factors of HVPTC.MethodsA systematic review of the literature for studies examining HVPTC was performed. Four databases (PubMed, Scopus, OVID, Cochrane library) were queried from inception of databases through March 20th, 2020.ResultsSixteen studies with 124 cases of HVPTC were included. The mean age for all patients was 52.3 years. HVPTC had a prevalence of 1.08% out of all PTC cases, with a mean tumor size of 3.1 cm. In 62% and 50% of cases, lymphovascular invasion and extrathyroidal extension were present, respectively. Follow-up data, with a mean of 49.9 months, revealed a 66% rate of lymph node metastasis and 23% rate of distant metastasis. Tumors with ≥30% hobnail morphology had a 2.6-fold increased odds of developing lymph node metastasis compared with <30% hobnail morphology, however did not differ in rates of distant metastasis. Patients ≥55 years old had a 4.5-fold increased odds of distant metastasis and a 4.7-fold increased odds of lymphovascular invasion over patients <55.ConclusionsHigh rates of locoregional and distant disease as well as high-risk pathological factors reveal the aggressive nature of HVPTC. Diagnostic criteria regarding percentage of hobnail morphology requires further refinement. Further studies are warranted in order to better understand how recognition of this high-risk variant impacts clinical treatment.
| S-EPMC8111367 | biostudies-literature