MiRNA Expression Pattern in Papillary Thyroid Cancer
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE191117 | GEO | 2022/05/26
REPOSITORIES: GEO
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Project description:Well-differentiated tumours (WDT) of the thyroid gland can be difficult to diagnose. Focal nuclear clearing can be suggestive of a papillary thyroid carcinoma (PTC), while questionable vascular or capsular penetration may raise the possibility of diagnosis of a follicular thyroid carcinoma (FTC). The recently proposed term “thyroid tumours of uncertain malignant potential” (TT-UMP) defines cases showing inconclusive morphological evidence of malignancy. We use microRNA (miRNA) expression profiling to analyze 42 well differentiated thyroid tumours including 7 follicular tumours of uncertain malignant potential (FT-UMP), 6 well differentiated tumours of uncertain malignant potential (WDT-UMP), 7 follicular thyroid adenomas (FTA), 5 follicular variant of papillary thyroid carcinoma (FV-PTC) 6 follicular thyroid carcinoma (FTC), and 11 conventional papillary thyroid carcinoma (C-PTC) with 6 C-PTC mutated for BRAFV600E (C-PTC-mut) and 5 not mutated: wild type (C-PTC-wt). Comparison of these 13 tumours of uncertain malignant potential (7 FT-UMP and 6 WDT-UMP) with those obtained from 16 PTC (11 C-PTC and 5 FV-PTC), 6 FTC and 7 FTA is performed in order to clarify the relationships between TT-UMP and the morphologically well characterized categories of thyroid tumours (i.e. C-PTC, FV-PTC, FTC and FTA). In first, each pathological sample (“L” for Lesional tissue) is compared with its matched control (“S” for Safe tissue) for the 42 patients (84 miRNA microarray slides). This control was taken from the same patient at a large distance from the tumour. Secondly, the perilesional tissue from the same patients but 2 (1 PTC and 1 adenoma, without enough RNA left) is compared to normal thyroid tissue (safe tissue reference) obtained from a patient who underwent total thyroidectomy for a laryngeal carcinoma that partially invaded the thyroid gland, to search for microRNA signatures of perilesional tissues (80 miRNA microarray slides).Experiments is performed with a miRNA microarray, referenced in GEO under the accession number GPL4717 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GPL4717). 42 Patients: 7 FT-UMP, 6 WDT-UMP, 7 FTA (+1 duplicate sample), 5 FV-PTC, 6 FTC (+ 2 duplicate samples), and 11 C-PTC. 44 dye-swap pairs and 1 with no dye swap pair for a total of 89 samples.
2011-08-21 | E-GEOD-15740 | biostudies-arrayexpress
Project description:Well-differentiated tumours (WDT) of the thyroid gland can be difficult to diagnose. Focal nuclear clearing can be suggestive of a papillary thyroid carcinoma (PTC), while questionable vascular or capsular penetration may raise the possibility of diagnosis of a follicular thyroid carcinoma (FTC). The recently proposed term “thyroid tumours of uncertain malignant potential” (TT-UMP) defines cases showing inconclusive morphological evidence of malignancy. We use microRNA (miRNA) expression profiling to analyze 42 well differentiated thyroid tumours including 7 follicular tumours of uncertain malignant potential (FT-UMP), 6 well differentiated tumours of uncertain malignant potential (WDT-UMP), 7 follicular thyroid adenomas (FTA), 5 follicular variant of papillary thyroid carcinoma (FV-PTC) 6 follicular thyroid carcinoma (FTC), and 11 conventional papillary thyroid carcinoma (C-PTC) with 6 C-PTC mutated for BRAFV600E (C-PTC-mut) and 5 not mutated: wild type (C-PTC-wt). Comparison of these 13 tumours of uncertain malignant potential (7 FT-UMP and 6 WDT-UMP) with those obtained from 16 PTC (11 C-PTC and 5 FV-PTC), 6 FTC and 7 FTA is performed in order to clarify the relationships between TT-UMP and the morphologically well characterized categories of thyroid tumours (i.e. C-PTC, FV-PTC, FTC and FTA). In first, each pathological sample (“L” for Lesional tissue) is compared with its matched control (“S” for Safe tissue) for the 42 patients (84 miRNA microarray slides). This control was taken from the same patient at a large distance from the tumour. Secondly, the perilesional tissue from the same patients but 2 (1 PTC and 1 adenoma, without enough RNA left) is compared to normal thyroid tissue (safe tissue reference) obtained from a patient who underwent total thyroidectomy for a laryngeal carcinoma that partially invaded the thyroid gland, to search for microRNA signatures of perilesional tissues (80 miRNA microarray slides).Experiments is performed with a miRNA microarray, referenced in GEO under the accession number GPL4717 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GPL4717).
2011-08-22 | GSE15740 | GEO
Project description:To comprehensively characterize microRNAs (miRNA) expression and their target genes in thyroid cancer, we performed next-generation sequencing expression analysis of this disease. Recent studies have found that only the most abundant microRNAs mediate significant target suppression. We sequenced small RNA from 8 papillary thyroid carcinomas (PTC) with paired samples of normal thyroid tissue. We found that only a small set of abundant miRNAs are differentially expressed after pair-wise comparison (12 upregulated and 8 downregulated) reaching the minimum threshold amount to repress target mRNAs. We integrated computational prediction of potential targets and mRNA sequencing from the paired normal and tumor thyroid tissues from the same eight patients with PTC. The integrated analyses identified a master microRNA regulatory network in PTC that is involved in essential biological processes such as thyroid differentiation. As both mature products of miR-146b (miR-146b-5p and -3p) were among the most abundant upregulated in tumors, we unveil their target genes and found that miR-146b-3p specifically binds to the 3`UTR of PAX8 and NIS, leading to an impaired translation of the proteins and subsequently decreasing the iodide uptake of the cells. Furthermore, we show that mir-146b and PAX8 regulate each other, describing a novel regulatory circuit that determines the differentiated phenotype of PTC. In conclusion, our integrative genomic analysis uncovers the target genes of two of the most upregulated miRNAs and highlights the importance of a miR-146b3p-PAX8-NIS regulatory circuit that determines thyroid differentiation in thyroid cancer. Samples from Papillary Thyroid Carcinoma tumors (n=8) and contralateral normal thyroid tissue from the same patient (n=8) were collected at the Biobank of the Hospital Universitario La Paz (Madrid, Spain). The clinical characteristics of patients are summarized in Table S1. Surgically removed tissues were quickly frozen in liquid nitrogen until analysis. The samples were snap frozen on dry ice and stored at -80°C.
2015-08-24 | E-GEOD-63511 | biostudies-arrayexpress
Project description:To comprehensively characterize microRNAs (miRNA) expression and their target genes in thyroid cancer, we performed next-generation sequencing expression analysis of this disease. Recent studies have found that only the most abundant microRNAs mediate significant target suppression. We sequenced small RNA from 8 papillary thyroid carcinomas (PTC) with paired samples of normal thyroid tissue. We found that only a small set of abundant miRNAs are differentially expressed after pair-wise comparison (12 upregulated and 8 downregulated) reaching the minimum threshold amount to repress target mRNAs. We integrated computational prediction of potential targets and mRNA sequencing from the paired normal and tumor thyroid tissues from the same eight patients with PTC. The integrated analyses identified a master microRNA regulatory network in PTC that is involved in essential biological processes such as thyroid differentiation. As both mature products of miR-146b (miR-146b-5p and -3p) were among the most abundant upregulated in tumors, we unveil their target genes and found that miR-146b-3p specifically binds to the 3`UTR of PAX8 and NIS, leading to an impaired translation of the proteins and subsequently decreasing the iodide uptake of the cells. Furthermore, we show that mir-146b and PAX8 regulate each other, describing a novel regulatory circuit that determines the differentiated phenotype of PTC. In conclusion, our integrative genomic analysis uncovers the target genes of two of the most upregulated miRNAs and highlights the importance of a miR-146b3p-PAX8-NIS regulatory circuit that determines thyroid differentiation in thyroid cancer.
2015-08-24 | GSE63511 | GEO
Project description:We show that numerous miRNAs are transcriptionally up-regulated in papillary thyroid carcinoma (PTC) tumors compared with unaffected thyroid tissue. Among the predicted target genes of the three most upregulated miRNAs (miRs 221, 222 and 146b), only less than 15% showed significant downexpression in transcript level between tumor and unaffected tissue. The KIT gene which is known to be downregulated by miRNAs 221 and 222 displayed dramatic loss of transcript and protein in those tumors that had abundant mir-221, mir-222, and mir-146b transcript. Experiment Overall Design: Total RNA was extracted from paired tumor and normal thyroid tissues from 9 PTC patients. The same set samples were applied to Custom miRNA microarray chips (OSU_CCC version 2.0) and Affymetrix HG-U133 plus 2 chips.
2007-09-01 | E-GEOD-3467 | biostudies-arrayexpress
Project description:The aim of this study was to conduct a baseline comparison of serum-circulating miRNA in prediabetic individuals with the distinction between those who later progressed to type 2 diabetes (T2DM) and those who did not. The expression level of 798 miRNAs using NanoString technology was examined. Spearman correlation, ROC curve analysis, and logistic regression modeling were performed. Gene ontology (GO), canonical pathways analysis were used to explore the biological functions of the miRNA target genes. The study revealed that 18 miRNAs were upregulated in serum samples of patients who later progressed to T2DM. Pathway analysis showed that miRNA target genes were mainly significantly enriched in neuroinflammation signaling, Myc mediated apoptosis signaling and tumoricidal function of hepatic natural killer (NK) cells. ROC analysis demonstrated that miR-491-5p, miR-1307-3p, and miR-298 can be introduced as a diagnostic tool for the prediction of T2DM (AUC=97.1%; 90.2%; 88.7%; respectively). Validation by qRT-PCR confirmed our findings. The results suggest that circulating miRNAs can potentially be used as predictive biomarkers of T2DM in prediabetic patients.
2020-07-21 | GSE148961 | GEO
Project description:Apart from alterations in the RET/PTC-RAS-BRAF pathway, comparatively little is known about the genetics of papillary thyroid carcinoma (PTC). We show that numerous miRNAs are transcriptionally up-regulated in PTC tumors compared with unaffected thyroid tissue. A set of 5 miRNAs including the 3 most upregulated ones (miRs 221, 222, 146) distinguished unequivocally between PTC and normal thyroid. Additionally, miR-221 was upregulated in unaffected thyroid tissue in several PTC patients, presumably an early event in carcinogenesis. Tumors in which the upregulation (11-19 fold) of miRs 221, 222 and 146 was strongest showed dramatic loss of KIT transcript and Kit protein. In five of 10 such cases this was associated with germline single nucleotide changes in the two recognition sequences in KIT for these miRNAs. We conclude that upregulation of several miRs and down regulation of KIT are involved in PTC pathogenesis, and that sequence changes in genes targeted by miRNAs can contribute to their downregulation.
2005-02-28 | E-TABM-68 | biostudies-arrayexpress
Project description:Introduction: MicroRNAs (miRNAs) in circulation have emerged as promising biomarkers. In this study we aimed to identify a circulating miRNA signature for osteoarthritis (OA) patients. Methods: Serum samples were collected from 12 primary OA patients and 12 healthy individuals and were screened using the Agilent Human miRNA Microarray. Receiver Operating Characteristic (ROC) curves were constructed to evaluate the diagnostic performance of the deregulated miRNAs. Expression levels of selected miRNAs were validated by quantitative Real-time PCR (qRT-PCR) in all serum samples and in articular cartilage samples from OA patients (n=12) and healthy individuals (n=7). Bioinformatics analysis was used to investigate the involved pathways and target genes of the above miRNAs. Results: We identified 279 differentially expressed miRNAs in the serum of OA patients compared to healthy controls. 205 (73.5%) were up-regulated and 74 (26.5%) down-regulated. ROC analysis revealed that 77 miRNAs had area under the curve (AUC)> 0.8 and p<0.05. Bioinformatics analysis in 7 out of the 77 selected miRNAs (hsa-miR-33b-3p, hsa-miR-4284, hsa-miR-671-3p, hsa-miR-663a, hsa-miR-140-3p, hsa-miR-150-5p and hsa-miR-1233-3p) revealed that their target genes were involved in multiple signaling pathways, among which FOXO, mTOR, pI3K/akt, lipid metabolism and TGF-β. A serum miRNA signature including three down-regulated miRNAs (hsa-miR-33b-3p, hsa-miR-671-3p and hsa-miR-140-3p) were also verified by qRT-PCR in OA patients. Furthermore, we found that hsa-miR-140-3p, hsa-miR-671-3p and potentially hsa-miR-33b-3p expression levels were consistently down-regulated in articular cartilage of OA patients compared to healthy individuals. Conclusions: A global miRNA serum signature was revealed in OA patients. We identified a three- miRNA signature in peripheral serum which could be potential osteoarthritis biomarkers.
2017-10-17 | GSE105027 | GEO
Project description:Although most thyroid tumours are benign, thyroid cancer represents the most common malignancy of the endocrine system, comprising mainly follicular and papillary thyroid carcinomas (FTC and PTC, respectively). Previous studies have shed some light on the molecular pathogenesis of thyroid cancer but there have not been any comprehensive mass spectrometry-based proteomic studies to reveal protein expression differences between thyroid tumours and the molecular alterations associated with tumour malignancy. We applied a label-free quantitative mass spectrometry analysis to compare normal thyroid tissue with the three most common tumours of the thyroid gland: follicular adenoma, follicular carcinoma and papillary carcinoma.
2017-05-03 | PXD002732 | Pride
Project description:MiRNAs regulate posttranscriptional gene expression and are widely implicated in the pathogenesis of complex diseases. We aim to elucidate miRNA regulation of the atrial mRNA signatures that associate with AF. This may provide novel mechanistical insights and candidate targets for therapies using miRNA mimics or antimiRs.
We present combined miRNAs-mRNAs sequencing in atrial tissues of patient without AF (n=22), with paroxysmal AF (n=22) and with persistent AF (n=20). MiRNA and mRNA signatures followed an ordinal scale from nonAF to paroxysmal to persistent AF patients. The previously reported mRNA sequencing identified 5228 differentially expressed genes involved in epithelial to mesenchymal transition, endothelial cell proliferation and extracellular matrix remodelling involving collagens, glycoproteins and proteoglycans. We discovered 103 differentially expressed miRNAs. Key downregulated miRNAs included miR-135b-5p, miR-138-5p, miR-200a-3p, miR-200b-3p and miR-31-5p and key upregulated miRNAs were miR-144-3p, miR-15b-3p, miR-182-5p miR-18b-5p, miR-4306 and miR-206. The expression levels of differentially expressed miRNAs were negatively correlated with the expression levels of their predicted target mRNAs. The downregulated miRNAs demonstrated a more profound transcriptome effect than the upregulated miRNAs. Upregulated biological processes enriched in miRNAs targets related to epithelial and endothelial cell migration and glycosaminoglycan biosynthesis, in line with the processes discovered by the mRNA sequencing analysis.
Combined analysis of miRNA and mRNA sequencing uncovered miRNAs with a broad transcriptional effect in human AF. Epithelial to mesenchymal transition and endothelial cell proliferation were processes controlled by downregulated miR-135b-5p, miR-138-5p, miR-200a-3p, miR-200b-3p and miR-31-5p, which in turn may contribute to (myo)fibroblast activation and structural remodeling.\
| EGAS00001005296 | EGA