Expression profiling identifies deregulated pathways and top diagnostic markers in papillary thyroid carcinoma
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ABSTRACT: Expression microarray was used to compare 57 PTC with a reference sample (pool of 9 adjacent normal thyroid tissue) and 4 PTC against 4 matched adjacent normal thyroid tissue. A quality control filter was applied based on Feature Extraction flags (empty spaces replacing values) Experiment condition, 61 PTC and 4 adjacent normal thyroid tissue samples obtained from total thyroidectomies were laleled with Cy3 and a pool of 9 adjacent normal thyroid tissue was labeled with Cy5. Samples Cy3 and Cy5 were mixed and hybridized at slide glasses Agilent 8x60k platform.
Project description:Expression microarray was used to compare 57 PTC with a reference sample (pool of 9 adjacent normal thyroid tissue) and 4 PTC against 4 matched adjacent normal thyroid tissue. A quality control filter was applied based on Feature Extraction flags (empty spaces replacing values)
Project description:Papillary thyroid cancer (PTC) accounts for the predominant histological types of all thyroid cancers. Additionally, 15% PTC with LNM are unfortunately associated with increased radioiodine resistance, distant metastasis, recurrence and increased mortality. Additionally, 15% PTC with LNM are unfortunately associated with increased radioiodine resistance, distant metastasis, recurrence and increased mortality.Two proteomics research has been implemented to investigate the molecular mechanisms involved in pathogenesis of PTC patients younger than 45 years with LNM and identified several candidate biomarker.However, until now there is no study to comprehensively investigate the differential expressed proteins (DEPs) in PTC patients older than age 45 years.
Project description:Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of Papillary Thyroid Cancer tissue sample and adjacent normal tissue. The goals of this study are to analysis the different circRNAs expression between Cancer tissue sample and adjacent normal tissue. Quantitative reverse transcription polymerase chain reaction (qRT–PCR) methods and to evaluate protocols for optimal high-throughput data analysis. We performed circRNA-seq in Papillary Thyroid Cancer tissue sample and adjacent normal tissue. We found that through the deep sequencing of four pairs PTC and adjacent nontumor tissues, we identified 16569 circRNAs, 720 circRNAs were differentials expressed, among them, 301 upregulated and 419 downregulated.
Project description:Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Histologically normal appearing tissue adjacent to the tumor (NAT) from PTC patients is commonly used as a control in thyroid cancer studies, but the molecular characteristics of NAT tissue are not well characterized. The aim of this study was to characterize the global gene expression profile of NAT and compare it with those of normal and tumor thyroid tissues. We performed RNA sequencing of three categories of thyroid tissue samples including NAT, normal thyroid (N), and PTC tumor (T). Transcriptome analysis shows that NAT presents a unique gene expression profile, which was not associated with sex and the presence of lymphocytic thyroiditis. Among the differentially expressed genes (DEGs) of NAT vs N, 247 coding genes and 6 noncoding genes have been reported as cancer genes, being involved in cell proliferation, apoptosis, and tumorigenesis. In addition, dysregulated expression of ribosomal and small RNAs was identified in NAT. IPA analyses revealed that “Cellular Response to Therapeutics, Cardiovascular Disease, Organismal Injury and Abnormalities, Cancer, and Cellular Movement” appeared as major dysregulated pathways in the NAT tissues. This study provides a comprehensive study of the PTC transcriptome, which provides improved insight into the complexity of gene expression changes during PTC tumorigenesis.
Project description:CircRNA deregulation could be a crucial event in thyroid carcinoma. To investigate circRNA signatures present in several papillary thyroid carcinoma (PTC) patients to complement our understanding of PTC pathogenesis. Using microarray technology, we screened the circRNA profiles in 3 pairs of PTC tumors and matching adjacent normal tissues. This study evaluated circRNAs expression profiles and their ability to serve as reliable biomarkers and new potential diagnostic and therapeutic targets for PTC
Project description:Thyroid ultrasound and ultrasound-guided fine-needle aspiration (USG/FNA) biopsy are currently used for diagnosing papillary thyroid carcinoma (PTC), but their detection limit could be improved by combining other biomarkers. To discover novel PTC biomarkers, we herein applied a GeLC-MS/MS strategy to analyze the proteome profiles of serum-abundant-protein-depleted FNA cystic fluid from benign and PTC patients, as well as two PTC cell line secretomes. From them, we identified 346, 488, and 2105 proteins, respectively. Comparative analysis revealed that 191 proteins were detected in the PTC but not the benign cystic fluid samples, and thus may represent potential PTC biomarkers. Among these proteins, 101 were detected in the PTC cell line secretomes, and seven of them (NPC2, CTSC, AGRN, GPNMB, DPP4, ERAP2, and SH3BGRL3) were reported in public PTC transcriptome datasets as having 4681 elevated mRNA expression in PTC. Immunoblot analysis confirmed the elevated expression levels of five proteins (NPC2, CTSC, GPNMB, DPP4, and ERAP2) in PTC versus benign cystic fluids. Immunohistochemical studies from near 100 pairs of PTC tissue and their adjacent non-tumor counterparts further showed that AGRN (n = 98), CTSC (n = 99), ERAP2 (n = 98) and GPNMB (n = 100) were significantly (p<0.05) overexpressed in PTC and higher expression levels of AGRN and CTSC were also significantly associated with metastasis and poor prognosis of PTC patients. Collectively, our results indicate that an integrated analysis of FNA cystic fluid proteome, cancer cell secretome and tissue transcriptome datasets represents a useful strategy for efficiently discovering novel PTC biomarker candidates.
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.
Project description:The dysregulation of circular RNAs (circRNAs) has been implicated in the development and progression of papillary thyroid cancer (PTC). In this study, we analyzed the dysregulated circRNA profile using PTC tissues and matched adjacent normal tissues by RNA-seq.
Project description:A comparison of profiles of normal thryoid tissue (NT), papillary thyroid carcinoma tissue (PTC) and anaplastic thyroid carcinoma tissue (ATC) was carried out to identify expression patterns specifically associated with analplastic thyroid carcinoma Keywords: Expression profile survey of normal tissue and tumor subtypes