Project description:Mice with thyroid-specific expression of oncogenic BRAF (Tg-Braf) develop papillary thyroid cancers (PTC) that are locally invasive and have well-defined foci of poorly differentiated thyroid carcinoma (PDTC). To investigate the PTC-PDTC progression, we performed a microarray analysis using RNA from paired samples of PDTC and PTC collected from the same animals by laser capture microdissection. Analysis of 8 paired samples revealed a profound deregulation of genes involved in cell adhesion and intracellular junctions, with changes consistent with an epithelial-mesenchymal transition (EMT). This was confirmed by IHC, as vimentin expression was increased and E-cadherin lost in PDTC compared to adjacent PTC. Moreover, PDTC stained positively for phospho-Smad2, suggesting a role for transforming growth factor-beta (TGFbeta) in mediating this process. Accordingly, TGFbeta induced EMT in primary cultures of thyroid cells from Tg-Braf mice, whereas wild-type thyroid cells retained their epithelial features. TGFbeta-induced Smad2 phosphorylation, transcriptional activity and induction of EMT required MAPK pathway activation in Tg-Braf thyrocytes. Hence, tumor initiation by oncogenic BRAF renders thyroid cells susceptible to TGFbeta-induced EMT, through a MAPK-dependent process. Comparing the transcription profiles of 8 pairs of murine poorly differentiated thyroid cancer and papillary thyroid cancer collected from the same animals by laser capture microdissection. Co-hybridizations were done in triplicate with a single dye flip.
Project description:We compared the expression profiles of papillary thyroid tumors from the Chernobyl Tissues Bank (CTB) with tumors from French patients with no history of exposure to radiations. Keywords: papillary thyroid cancer vs. patient-matched healthy adjacent thyroid thyroid papillary cancer vs. patient-matched adjacent nontumor thyroid tissues. -14 tumors from France -12 tumors from Ukraine
Project description:We compared the expression profiles of papillary thyroid tumors from the Chernobyl Tissues Bank (CTB) with tumors from French patients with no history of exposure to radiations. Keywords: papillary thyroid cancer vs. patient-matched healthy adjacent thyroid
Project description:Papillary thyroid carcinoma (PTC) is the most common malignant phenotype of thyroid cancer, with a rapidly increasing number of new cases globally. Multifocality is a common phenomenon in patients with PTC. The tumor microenvironment (TME) plays a pivotal role in cancer progression in papillary thyroid carcinoma (PTC), yet the composition and phenotype of cells within TME in bilateral PTCs are poorly understood.
Project description:Tumor microenvironment heterogeneity sheltered our understanding of papillary thyroid cancer. However, molecular characteristics of papillary thyroid cancer has not been reported at single cell resolution. The immunological link between papillary thyroid cancer and Hashimoto's thyroiditis is also in doubt.We identified 24 cell clusters in human papillary thyroid cancer based on their heterogeneous gene expression pattern. Follicular epithelial cell subsets in papillary thyroid cancer with Hashimoto's thyroiditis and papillary thyroid cancer without Hashimoto's thyroiditis showed different malignant level. Machine learning model identified potential biomarker to evaluate tumor epithelial cell development. Together with immunostaining, lymphocytes heterogeneity indicated an obvious B cell infiltration pattern in papillary thyroid cancer with Hashimoto's thyroiditis. Additionally, trajectory analysis of B cell and plasma cell suggest the migration potential from normal adjacent tissue of Hashimoto's thyroiditis to papillary thyroid cancer tissue. Our results provide the first single cell landscape of Papillary thyroid cancer. Single cell data resource of Papillary thyroid cancer with Hashimoto's thyroiditis promote our understanding of molecular heterogeneity and immunological link between papillary thyroid cancer and Hashimoto's thyroiditis.
Project description:Papillary thyroid carcinoma (PTC), the most common form of thyroid carcinomas, is a well-differentiated tumor and accounts for about 80% of all thyroid carcinomas. With the advantage of providing comprehensively analysis of global proteins in samples, proteomics techniques are increasingly applied in the field of identifying novel biomarkers in thyroid cancer. In this study, we conducted a TMT labeling-based quantitative proteomics analysis and bioinformatics analysis to compare the alternation of global proteins in tumor tissues and para-tumor tissues between PTC with LNM and without LNM.
Project description:Radioiodine refractory differentiated thyroid cancer (RR-DTC) is the main factor affecting the overall survival rate of thyroid cancer clinically. In order to investigate its underlying molecular mechanism of pathogenesis with the hope to explore novel therapeutic targets for clinical treatment, we performed a comparative proteomic analysis in tumor tissue of patients with RR-DTC and papillary thyroid cancer.
Project description:Experiment a) Establishment of expression profiles in conventional papillary thyroid carcinomas (PTCs) with a BRAF mutation vs. PTCs without a BRAF mutation and using normal thyroid (TN) specimens as reference. Experiment b) Establishment of expression profiles in follicular adenomas (FAs) of the thyroid and follicular variant of papillary thyroid carcinomas (FVPTCs).
Project description:BACKGROUND. Poorly-differentiated (PDTC) and anaplastic (ATC) thyroid cancers are rare and frequently lethal tumors, which so far have not been subjected to comprehensive genetic characterization. METHODS. We performed next generation sequencing of 341 cancer genes in 117 PDTCs and ATCs, and a transcriptomic analysis of a representative subset of 37 tumors. Results were analyzed in the context of The Cancer Genome Atlas (TCGA) study of papillary thyroid cancers (PTC). RESULTS. ATCs have a greater mutation burden than PDTCs, and higher mutation frequency of TP53, TERT promoter, PI3K/AKT/mTOR pathway effectors, SWI/SNF subunits and histone methyltransferases. BRAF and RAS are the predominant drivers, and dictate remarkably distinct tropism for nodal vs. distant metastases in PDTC. RAS and BRAF sharply distinguish between PDTCs defined by the Turin (PDTC-Turin) vs. MSKCC (PDTC-MSK) criteria, respectively. Mutations of EIF1AX, a component of the translational preinitiation complex, are markedly enriched in PDTCs and ATCs, and have a striking pattern of co-occurrence with RAS. TERT promoter mutations are rare and subclonal in PTCs, whereas they are clonal and highly prevalent in advanced cancers. Application of the TCGA-derived BRAF-RAS score (a measure of MAPK transcriptional output) shows a preserved relationship with BRAF/RAS mutation in PDTCs, whereas ATCs are BRAF-like irrespective of driver mutation. CONCLUSIONS. These data support a model of tumorigenesis whereby PDTCs and ATCs arise from well-differentiated tumors through the accumulation of key additional genetic abnormalities, many of which have prognostic and possible therapeutic relevance. The widespread genomic disruptions in ATC compared to PDTC underscore their greater virulence and higher mortality. 37 tumor specimens, including 17 poorly-differentiated and 20 anaplastic thyroid cancers were expression-profiled with Affymetrix U133 plus 2.0 array