Imprinted gene detection effectively improves the diagnostic accuracy for papillary thyroid carcinoma
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ABSTRACT:
SUBMITTER: Chen Y
PROVIDER: S-EPMC10953243 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:Papillary thyroid carcinoma (PTC) is heterogeneous and its molecular characteristics remain elusive. We integrated transcriptomic sequencing, genomic analysis and clinicopathologic information from 582 tissue samples of 216 PTC and 75 benign thyroid nodule (BTN) patients. We discovered four subtypes of PTC including Immune-enriched Subtype, BRAF-enriched Subtype, Stromal Subtype and CNV-enriched Subtype. Molecular subtypes were validated in an external cohort of 497 PTC cases from the TCGA. Tumors in the Immune-enriched Subtype showed higher immune infiltration and overexpression of immune checkpoints, whilst BRAF-enriched Subtype showed a higher tendency for extrathyroidal extension and more advanced TNM stage. Key oncogenes including LRRK2, SLC34A2, MUC1, FOXQ1 and KRT19 were overexpressed and enriched in oncogenic MAPK and PI3K/AKT signaling pathways in BRAF-enriched subtype. Further analysis of BRAF-enriched Subtype identified three subclasses with different degrees of malignancies. We also uncovered the molecular link of the initiation and progression from BTN to subtypes of PTC using trajectory analysis. Moreover, a 20-gene expression signature was generated for differential diagnosis of PTC from BTN patients. Together, our work identified previously unreported molecular subtypes of PTC, offering opportunities to stratify patients into optimal treatment plans based on molecular subtyping.
| S-EPMC9674518 | biostudies-literature
Project description:Thyroid nodules (TNs) represent a common scenario. More accurate pre-operative diagnosis of malignancy has become an overriding concern. This study incorporated demographic, serological, ultrasound, and biopsy data and aimed to compare a new diagnostic prediction model based on Back Propagation Neural Network (BPNN) with multivariate logistic regression model, to guide the decision of surgery. Records of 2,090 patients with TNs who underwent thyroid surgery were retrospectively reviewed. Multivariate logistic regression analysis indicated that Bethesda category (OR=1.90, P<0.001), TIRADS (OR=2.55, P<0.001), age (OR=0.97, P=0.002), nodule size (OR=0.53, P<0.001), and serum levels of Tg (OR=0.994, P=0.004) and HDL-C (OR=0.23, P=0.001) were statistically significant independent differentiators for patients with PTC and benign nodules. Both BPNN and regression models showed good accuracy in differentiating PTC from benign nodules (area under the curve [AUC], 0.948 and 0.924, respectively). Notably, the BPNN model showed a higher specificity (88.3% vs. 73.9%) and negative predictive value (83.7% vs. 45.8%) than the regression model, while the sensitivity (93.1% vs. 93.9%) was similar between two models. Stratified analysis based on Bethesda indeterminate cytology categories showed similar findings. Therefore, BPNN and regression models based on a combination of demographic, serological, ultrasound, and biopsy data, all of which were readily available in routine clinical practice, might help guide the decision of surgery for TNs.
| S-EPMC9483149 | biostudies-literature
Project description:To assess their utility in routine neuropathology, we prospectively integrated DNA methylation-based CNS tumor classification and targeted gene panel sequencing of tumor and constitutional DNA with blinded neuropathological reference diagnostics for a population-based cohort of > 1,200 newly-diagnosed pediatric patients.
2023-01-30 | GSE215240 | GEO
Project description:Papillary thyroid carcinomas are the most common thyroid cancers and constitute more than 70% of thyroid malignancies. The most common etiologic factor is radiation, but genetic susceptibility and other factors also contribute to the development of papillary thyroid carcinoma. The most common variants include conventional, follicular variant and tall cell variant. However, many other uncommon variants have been described including oncocytic, columnar cell, diffuse sclerosing and solid forms. Immunohistochemical staining with TTF-1 and thyroglobulin is very useful in confirming the diagnosis of papillary thyroid carcinoma especially in metastatic sites. Markers such as HBME-1 and CITED1 can assist in separating some difficult cases of follicular variants of papillary thyroid carcinomas from follicular adenomas. Molecular studies have shown that the BRAF V600E mutation is found mainly in papillary and anaplastic thyroid carcinomas. Other molecular markers such as HMGA2 and insulin-like growth factor II mRNA binding protein 3 have been used recently as molecular tests to separate papillary thyroid carcinoma and its variants from follicular adenomas and other benign thyroid nodules.
| S-EPMC3037461 | biostudies-literature
Project description:BackgroundAs a rare but aggressive papillary thyroid carcinoma (PTC) variant, the genetic changes of hobnail variant of PTC (HVPTC) are still unclear.ResultsThe prevalence of HVPTC was 1.69% (18/1062) of all PTC diagnosed in our cohort. 73 samples from 55 patients (17 HVPTC, 26 CPTC, 7 PDTC and 5 ATC) were successfully analyzed using targeted NGS with an 18-gene panel. Thirty-seven mutation variant types were identified among 11 genes. BRAF V600E mutation was the most common mutation, which is present in almost all HVPTC samples (16/17, 94%), most CPTC samples (20/26, 77%), and none of the ATC and PDTC samples. TERT promoter mutation (C228T) was identified in 2 ATC and one HVPTC patient. RAS and TP53 mutation are almost exclusively present among ATC and PDTC samples although TP53 mutation was also observed in 3 HVPTC patients. Six different GNAS mutations were identified among 8 CPTC patients (31%) and none of the HVPTC patients. The only patient who died of disease progression harbored concomitant TERT C228T mutation, BRAF V600E mutation and TP53 mutation.MethodsHVPTC cases were identified from a group of 1062 consecutive surgical specimens diagnosed as PTC between 2000 and 2010. Targeted next-generation sequencing (NGS) was applied to investigate the mutation spectrum of HVPTC, compared to classical PTC (CPTC), poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC).ConclusionAs an aggressive variant of PTC, HVPTC has relatively specific molecular features, which is somewhat different from both CPTC and ATC/PDTC and may underlie its relatively aggressive behavior.
| S-EPMC5400643 | biostudies-literature
Project description:BackgroundThe incidence of node metastases in papillary thyroid carcinoma (PTC) is high, ranging from 20% to 90%. Prophylactic central lymph node compartment dissection (CLND), suggested from the latest guidelines for high-risk tumors, meets resistance due to the high incidence of postoperative complications. Recently, new molecular biologic techniques, such as One Step Nucleic Acid Amplification (OSNA), have spread widely, allowing to quickly isolate, amplify and quantify mRNA encoding for proteins selectively present in neoplastic cells, as Cytokeratine-19. The aim of this study is to evaluate the application of OSNA to intraoperative diagnosis of node metastases of PTC.MethodsWe included in the study patients with preoperative diagnosis of PTC; from each patient one or more lymph nodes were collected. To assess OSNA accuracy, each lymph node was divided into two halves: the first one was analysed with histopathological and immunohistochemical examination, whereas the second was studied with OSNA.ResultsTwenty-six lymph nodes from 13 patients were included in the study. Overall, OSNA sensitivity was 87.5%, specificity 94.4%, positive predictive value 87.5%, negative predictive value 94.4% and accuracy 92.8%.Discussion and conclusionOSNA is effective in detecting lymph node metastases of PTC. Considering the high risk of complications in CLND, and the uncertain prognostic value of lymph node metastases of PTC, OSNA seems to be a promising tool to identify intraoperatively patients who may benefit from CLND.
| S-EPMC6717061 | biostudies-literature
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) 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.
2014-11-01 | E-GEOD-50901 | biostudies-arrayexpress
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)
2014-11-01 | GSE50901 | GEO
Project description:BackgroundAccurate assessment of lateral cervical lymph node metastasis (LLNM) involvement is important for treating papillary thyroid carcinoma (PTC). Thyroglobulin is associated with LLNM, but there may be differences in the diagnostic value of serum thyroglobulin (sTg) and fine needle aspiration washout fluid thyroglobulin (FNA-Tg). Herein, we investigated the optimal cutoff value (OCV) of sTg and FNA-Tg and their diagnostic performance.MethodsWe enrolled 116 PTC patients who underwent radical resection of thyroid carcinoma with lateral cervical lymph node dissection at the Affiliated Hospital of Zunyi Medical University from June 2018 to July 2022. We used the receiver operating characteristic (ROC) curve analysis to determine the OCV for sTg and FNA-Tg to diagnose LLNM in PTC patients. We also evaluated the performance of FNA-Tg, sTg, fine needle aspiration cytology (FNAC), and their combinations for diagnosis. Pathological results were the gold standard.ResultsWe performed 125 lymph node dissections, 106 had metastasis, and 19 did not. The OCV for sTg was 17.31 ng/mL [area under the curve (AUC) =0.760, sensitivity =78.30%, specificity =73.68%, and accuracy =77.60%]. Meanwhile, the OCV for FNA-Tg was 4.565 ng/mL (AUC =0.948, sensitivity =89.62%, specificity =100%, and accuracy =91.20%). The combination of FNAC and FNA-Tg presented the greatest diagnostic performance for LLNM detection in PTC patients. Moreover, serum antithyroglobulin antibody (TgAb) was not correlated with sTg or FNA-Tg levels.ConclusionsThe cutoff value for the diagnosis of LLNM in PTC are sTg >17.31 ng/mL or FNA-Tg >4.565 ng/mL. The combination method of FNA-Tg and FNAC is the most optimal choice for the diagnosis of LLNM and is highly recommended for further clinical application.
| S-EPMC10928643 | biostudies-literature
Project description:Papillary thyroid carcinoma (PTC) is clinically heterogeneous. Apart from an association with ionizing radiation, the etiology and molecular biology of PTC is poorly understood. We used oligo-based DNA arrays to study the expression profiles of eight matched pairs of normal thyroid and PTC tissues. Additional PTC tumors and other tissues were studied by reverse transcriptase-PCR and immunohistochemistry. The PTCs showed concordant expression of many genes and distinct clustered profiles. Genes with increased expression in PTC included many encoding adhesion and extracellular matrix proteins. Expression was increased in 8/8 tumors for 24 genes and in 7/8 tumors for 22 genes. Among these genes were several previously known to be overexpressed in PTC, such as MET, LGALS3, KRT19, DPP4, MDK, TIMP1, and FN1. The numerous additional genes include CITED1, CHI3L1, ODZ1, N33, SFTPB, and SCEL. Reverse transcriptase-PCR showed high expression of CITED1, CHI3L1, ODZ1, and SCEL in 6/6 additional PTCs. Immunohistochemical analysis detected CITED1 and SFTPB in 49/52 and 39/52 PTCs, respectively, but not in follicular thyroid carcinoma and normal thyroid tissue. Genes underexpressed in PTC included tumor suppressors, thyroid function-related proteins, and fatty acid binding proteins. Expression was decreased in 7/8 tumors for eight genes and decreased in 6/8 tumors for 19 genes. We conclude that, despite its clinical heterogeneity, PTC is characterized by consistent and specific molecular changes. These findings reveal clues to the molecular pathways involved in PTC and may provide biomarkers for clinical use.
| S-EPMC64980 | biostudies-literature