RNA sequencing profiles for thyroid tumor tissue specimens
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE138042 | GEO | 2019/12/01
REPOSITORIES: GEO
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Project description:The inherent diagnostic limitations of thyroid fine needle aspiration (FNA), especially in the “indeterminate” category, can be partially overcome by molecular analyses. We aimed at the identification of miRNAs that could be used to improve the discrimination of indeterminate FNAs. miRNA expression profiling was performed for 17 follicular carcinomas (FTCs) and 8 follicular adenomas (FAs). The microarray results underwent cross-comparison using three additional microarray data sets. Candidate miRNAs were validated by qPCR in an independent set of 32 FTCs and 46 FAs. Sixty-eight differentially expressed miRNAs were identified. Thirteen miRNAs could be confirmed by cross comparison. A two-miRNA-classifier was established improving the diagnostic applicability and resulted in a sensitivity of 82% and a specificity of 49%. We present a classifier that has the potential to be successfully evaluated in cytology material for its capability to discriminate (mutation negative) indeterminate cytologies and thereby improving the pre-surgical diagnostics of thyroid nodules. miRNA expression profiling was performed for 17 follicular carcinomas (FTCs) and 8 follicular adenomas (FAs). All samples are independent, coming from different patients.
2014-10-07 | E-GEOD-62054 | biostudies-arrayexpress
Project description:The inherent diagnostic limitations of thyroid fine needle aspiration (FNA), especially in the “indeterminate” category, can be partially overcome by molecular analyses. We aimed at the identification of miRNAs that could be used to improve the discrimination of indeterminate FNAs. miRNA expression profiling was performed for 17 follicular carcinomas (FTCs) and 8 follicular adenomas (FAs). The microarray results underwent cross-comparison using three additional microarray data sets. Candidate miRNAs were validated by qPCR in an independent set of 32 FTCs and 46 FAs. Sixty-eight differentially expressed miRNAs were identified. Thirteen miRNAs could be confirmed by cross comparison. A two-miRNA-classifier was established improving the diagnostic applicability and resulted in a sensitivity of 82% and a specificity of 49%. We present a classifier that has the potential to be successfully evaluated in cytology material for its capability to discriminate (mutation negative) indeterminate cytologies and thereby improving the pre-surgical diagnostics of thyroid nodules.
2014-10-07 | GSE62054 | GEO
Project description:ATC are among the most lethal malignancies, for which there is no effective treatment. ATC global gene expression was profiled and compared to normal thyroid tissues, in order to elucidate the molecular alterations contributing to ATC development, and to identify novel therapeutic targets. RNA were extracted from 5 ATC samples. 3 samples were obtained at time of surgery, and were immediately frozen in liquid nitrogen. The RNA from the remaining samples were collected during fine-needle aspiration biopsies, being conserved in RLT buffer (RNeasy Mini Kit, Quiagen) and maintained at -70ºC. RNA were also extracted from 3 normal thyroid samples, which were collected during surgery, taken from the opposite lobe of thyroid tumors. We also hybridized a commercial pool of human thyroid total RNA (BD Bioscience).
2013-12-07 | E-GEOD-53072 | biostudies-arrayexpress
Project description:PURPOSE: Thyroid cancer is frequently difficult to diagnose due to an overlap of cytological features between malignant and benign nodules. This overlap leads to unnecessary removal of the thyroid in patients without cancer. While providing some improvement over cytopathologic diagnostics, molecular methods frequently fail to provide a correct diagnosis for thyroid nodules. These approaches are based on the difference between malignant nodules and normal adjacent thyroid tissue and assume that normal thyroid tissues are the same as benign nodules. However, in contrast to normal thyroid tissues, benign thyroid nodules can contain genetic alterations that can be found in cancerous nodules. PATIENTS AND METHODS: For the development of a new molecular diagnostic test for thyroid cancer, we evaluated DNA methylation in 109 thyroid tissues by using genome wide single base resolution DNA methylation analysis (Reduced Representation Bisulfite Sequencing). The test was validated in the retrospective cohort containing 64 thyroid nodules. RESULTS: By conducting Reduced Representation Bisulfite Sequencing in 109 thyroid specimens, we found significant differences between normal tissue, benign nodules, and cancer. Based on tissue-specific epigenetic signatures for benign and malignant nodules, we developed a new epigenetic approach for thyroid diagnostics. According to the validation cohort, our test has an estimated specificity of 97% (95% CI, 80 to 100), sensitivity of 100% (95% CI, 86 to 100), PPV of 97% (95% CI, 82-100), NPV of 100% (95%, 85 to 100). CONCLUSION: These data show that epigenetic testing can provide outstanding diagnostic accuracy for thyroid nodules by evaluating tissue specific DNA methylation.
2018-11-30 | GSE107738 | GEO
Project description:While thyroid nodules per se are frequent (4%–50%), thyroid cancer is rare (∼5% of all thyroid nodules). The minimally invasive Fine Needle Aspiration Cytology (FNAC) is the current gold standard for the diagnosis thyroid nodule malignancy. However, proper discrimination of follicular neoplasias often require more invasive diagnostic techniques. To develop a novel molecular classification system for thyroid cancer malignancy, we performed a genome-wide epigenetic profiling of 54 fresh frozen Follicular like thyroid samples using the Illumina Human DNA Methylation EPIC platform.
2022-09-01 | E-MTAB-10906 | biostudies-arrayexpress
Project description:Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer among women worldwide. It is confirmed mainly by fine-needle aspiration biopsy (FNAB), an invasive diagnostic method. The key proteins responsible for thyroid hormone biosynthesis are glycosylated. Changes in site-specific glycosylation are associated with thyroid cancer. Integrated quantitative proteomic and glycoproteomic analyses of body fluids from patients with PTC may identify potential noninvasive biomarkers, improve diagnostic accuracy, and elucidate the basic mechanisms of tumor development. In the present study, we demonstrated a novel integrated method of body fluid proteome and glycoproteome analysis. We showed that it is highly reproducible and fast. It may also quantitatively profile protein glycosylation. Intact N-glycopeptides from the urine and plasma of healthy controls (HC), PTC, and PTC with Hashimoto’s thyroiditis (PHT) were enriched by hydrophilic interaction liquid chromatography. Sialic acid was removed from the N-glycopeptides with trifluoroacetic acid and heat. The desialo-N-glycopeptides were analyzed by HCD-MS/MS using stepped collision energies and several search engines for quantitative profiling. Ninety-two altered proteins and 134 intact N-glycopeptides were isolated from the plasma and urine samples of the three groups (90 samples from 15 subjects). To the best of our knowledge, this study is the first to compare the plasma and urinary proteomes and glycoproteomes of HC, PTC, and PHT. Moreover, we revealed a novel indicator (ratio of fucosylated to non-fucosylated N-glycopeptide or F/NF) through desialo-N-glycopeptide analysis. These differently expressed glycoproteins and F/NF may serve as biomarkers contributing to clinical cancer diagnostics and could be used to improve diagnostic accuracy noninvasively.
2019-12-09 | PXD015360 | Pride
Project description:Thyroid cancer is a common endocrine malignancy; however, its diagnosis is not straightforward. The current gold standard for diagnosing thyroid cancer is fine needle aspiration biopsy (FNAB), but when cytological analysis does not provide viable results or samples belong to less defined categories of diagnosis, patients are often referred to diagnostic surgery. Given that not all these nodules require removal, nor all of them are malignant, patients would not necessarily require surgery had the initial FNAB diagnosis been more conclusive. There is therefore a lack of reliable and specific biomarkers for thyroid cancer malignancy, that can complement and improve the current diagnosing methods. “Omics” approaches have gained much attention in the last decade in the field of biomarker discovery for diagnostic and prognostic characterization of various pathophysiological conditions. In this project, proteomics and metabolomics approaches were applied to the same thyroid nodules from patients with benign and malignant lesions. Tissue analysis provided several interesting biomarkers by both proteomics and metabolomics. The combination of these results demonstrated the high energetic and biomass demand of cancer cells, as well as a biomarker panel including 2 free peptides and 2 proteins with high sensitivity and specificity. Together, these results have contributed to increasing the knowledge of thyroid cancer phenotype and corresponding biochemical profiles, as well as providing potential biomarkers for malignancy, and improving diagnostic methodologies.
2023-10-24 | PXD035583 | Pride
Project description:Purpose: To clinically and proteomically profile a fine-needle aspirate biopsy (FNAB) from a single in situ cold thyroid nodule (CTN). Experimental Design: The FNAB lysate was digested with trypsin, and analysed by LC-MSMS on an LTQ Orbitrap Velos. Remaining peptides were separated by reversed-phase chromatography and fractions analysed as technical duplicates. Identified proteins were analysed by Gene Ontology and protein abundance were calculated using the Top3 label-free method. The proteomic data was complemented with ultrasonography and scintigraphy of the thyroid gland; and cytology of the CTN FNAB. Results: Sixty seven and 2,595 non-redundant protein groups (2 unique peptides) were identified from unfractionated and fractionated CTN FNAB, respectively. Label-free protein abundance ranged over 6 orders of magnitude from the most abundant proteins, haemoglobin and thyroglobulin; to the low-abundance protein SON. Many previously-reported markers of thyroid cancer were in the top 23% of the identified proteins. GO analysis revealed high-enrichment for extracellular vesicular exosome and vesicle (cellular component); regulation of biological quality (biological processes); and structural molecule activity (molecular function). Conclusions and Clinical Significance: The CTN was clinically-classified as benign. Proteomic data from FNAB can provide additional diagnostic candidates indicative of benign or cancerous CTN without the need for invasive surgical intervention.
2017-10-26 | PXD001978 | Pride
Project description:RNA sequencing profiles for thyroid tumor tissue specimens
| PRJNA574551 | ENA
Project description:BACKGROUND: Following fine needle aspiration, 15-30% of thyroid nodules are not clearly benign or malignant. These cytologically indeterminate nodules are often referred for diagnostic surgery, though most prove benign. A novel diagnostic test measuring the expression of 167 genes has shown promise in improving pre-operative risk assessment. We evaluated this test in a prospective, multicenter study. METHODS: Over 19 months, we performed a prospective study at 49 clinical sites enrolling 3,789 patients and collecting 4,812 samples from thyroid nodules >1cm requiring evaluation. We obtained 577 cytologically indeterminate aspirates with corresponding histopathology of excised lesions on 413. Central blinded histopathologic review served as the reference (“gold”) standard. After applying inclusion criteria, gene expression classifier results were obtained for 265 indeterminate nodules used in this analysis, and performance was calculated. RESULTS: 85 of 265 indeterminate nodules were malignant. The gene expression classifier correctly identified 78 of 85 as ‘suspicious’ (92% sensitivity, [84%-97%] 95% CI). Specificity was 52%, [44%-59%]. The negative predictive value was 95%, 94%, and 85%, respectively, for aspirates with AUS/FLUS, FN/SFN, or ‘suspicious’ cytology. Analysis of 7 false negative cases revealed 6 with a paucity of thyroid follicular cells, suggesting that insufficient sampling of the nodule had occurred. CONCLUSIONS: Though individualized clinical care is recommended, these data support consideration of a conservative approach for most patients with indeterminate FNA cytology and benign gene expression classifier results. 265 cytologically indetermine samples, 47 cytologically benign and 55 cytologically malignant samples
2012-06-24 | E-GEOD-34289 | biostudies-arrayexpress