A targeted proteomics assay for the preoperative diagnosis of thyroid nodules
Ontology highlight
ABSTRACT:
INSTRUMENT(S):
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Thyroid Nodule
DISEASE(S): Thyroid Cancer
SUBMITTER: 
Tiannan Guo
LAB HEAD: Tiannan Guo
PROVIDER: PXD046014 | Pride | 2026-01-21
REPOSITORIES: Pride
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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
Project description:Understanding thyroid aging is essential for deciphering its physiological and pathological alterations, yet the causal relationship between aging and thyroid disease remains poorly characterized. We conducted a comprehensive proteomic analysis of 6109 thyroid tissues across ages 8-87 from 22 clinical centers (retrospective and prospective cohorts). Using a machine learning-based biological aging clock, we quantified accelerated aging phenotypes in pathological tissues, including benign and malignant nodules. We identified linear and non-linear age-associated proteins and pathways related to metabolism, immune response, and extracellular matrix organization remodeling, with critical transitions observed during the third, sixth, and eighth decades. Cross-species analysis of mouse and monkey tissues uncovered conserved aging markers. Intervention studies suggested that low-protein diets delay thyroid aging in mice, and therapeutic drug screening identified potential anti-tumor candidates. This study establishes the first organ-specific thyroid aging clock, linking tumorigenesis to accelerated aging, and proposing dietary interventions for thyroid longevity.
2025-11-04 | PXD061183 | Pride
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.
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Project description:Background: Fine needle aspiration biopsy (FNAB) is the gold-standard procedure for diagnosing malignant thyroid nodules. Indeterminate cytology is identified in 10-40% of cases and molecular testing may guide management in this setting. Current commercial options are expensive, and are either sensitive or specific. The aim of this study was to utilize next generation sequencing (NGS) technology to identify informative diversities in the microRNA (miRNA) expression profile of benign versus malignant thyroid nodules. Methods: Ex-vivo FNAB samples were obtained from thyroid specimens of patients that underwent thyroidectomy at a referral center. miRNA levels were determined using NGS and multiplexing technologies. Statistical analyses identified differences between normal and malignant samples and miRNA expression profiles that associate with malignancy were established. The accuracy of the miRNA signature in predicting histological malignancy was validated using a group of patient specimens with indeterminate cytology results. Results: 274 samples were obtained from 102 patients undergoing thyroidectomy. Of these samples, 71% were benign and 29% were malignant. Nineteen miRNAs were identified as statistically different between benign and malignant samples and were used to classify 35 additional nodules with indeterminate cytology (validation). The miRNA panel’s sensitivity, specificity, negative and positive predictive values and overall accuracy were 91%, 100%, 87%, 100% and 94%, respectively. Conclusion: Using NGS technology we identified a panel of 19 miRNAs that may be utilized to distinguish benign from malignant thyroid nodules with indeterminate cytology. Impact: Our panel may classify indeterminate thyroid nodules at higher accuracy than commercially available molecular tests.
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2021-04-12 | PXD024904 | Pride
Project description:Thyroid nodules occur in about 60% of the population. Current diagnostic strategies, however, often fail at distinguishing malignant nodules before surgery, thus leading to unnecessary, invasive treatments. As proteins are involved in all physio/pathological processes, a proteome investigation of biopsied nodules may help correctly classify and identify malignant nodules and discover therapeutic targets. Quantitative mass spectrometry data-independent acquisition (DIA) enables highly reproducible and rapid throughput investigation of proteomes. An exhaustive spectral library of thyroid nodules is essential for DIA yet still unavailable. This study presents a comprehensive thyroid spectral library covering five types of thyroid tissue: multinodular goiter, follicular adenoma, follicular and papillary thyroid carcinoma, and normal thyroid tissue. Our library includes 925,330 transition groups, 157,548 peptide precursors, 121,960 peptides, 9941 protein groups, and 9826 proteins from proteotypic peptides. This library resource was evaluated using three papillary thyroid carcinoma samples and their corresponding adjacent normal thyroid tissue, leading to effective quantification of up to 7863 proteins from biopsy-level thyroid tissues.
2022-05-20 | PXD026395 | Pride
Project description:Preoperative Diagnosis of Benign Thyroid Nodules with Indeterminate Cytology
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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:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
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