Gene expression profiling of papillary thyroid cancer from central and invasive regions
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE83560 | GEO | 2017/06/09
SECONDARY ACCESSION(S): PRJNA326345
REPOSITORIES: GEO
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Project description:Papillary thyroid cancers (PTC) that invade into local structures are associated with a poor prognosis, but the mechanisms for PTC invasion are incompletely defined limiting the development of new therapies. To characterize biological processes involved in PTC invasion, we analyzed the gene expression profiles of microscopically dissected intratumoral samples from central and invasive regions of seven widely invasive PTCs and normal thyroid tissue by oligonucleotide microarray and performed confirmatory expression and functional studies. In comparison to the central regions of primary PTCs, the invasive fronts overexpressed TGF ï¢ï� ï¬ï� NFï«b and integrin pathway members, and regulators of small G-proteins and CDC42. Moreover, reduced levels of mRNAs encoding proteins involved in cell-cell adhesion and communication were identified, consistent with epithelial-to-mesenchymal transition (EMT). To confirm that aggressive PTCs were characterized by EMT, 35 additional PTCs were examined for expression of vimentin, a hallmark of EMT. Overexpression of vimentin was associated with PTC invasion and nodal metastasis. Functional, in vitro studies demonstrated that vimentin was required for the development and maintenance of both a mesenchymal morphology and invasiveness in thyroid cancer cells. We conclude that EMT is a common mechanism of PTC invasion and that vimentin regulates thyroid cancer EMT in vitro. Experiment Overall Design: Total RNA was obtained from all 7 central and invasion regions, as well as from 4 of 7 normal tissues. In addition, the comparison of central vs. normal tissues were compared to 9 paired central and normal samples from The Ohio State University tumor bank simultaneously analyzed using the same methods
2008-06-14 | E-GEOD-6004 | biostudies-arrayexpress
Project description:Paillary thyroid cancer (PTC) is the most common type of thyroid malignancy. Extrathyroidal invasion (ETİ), lymph node metastasis, and distance organ metastasis is poor prognostic factor in PTC. The metastasis is still a leading cause of papillary thyroid cancer death. The early detection of metastatic signature is crucial for identification of thyroid cancer prognosis and personalized therapeutic strategies. In the present study, we present thyroid cancer metastasis and invasivenes related miRNAs identified by comprehensive miRNA expression profiling of formalin-fixed paraffin embedded (FFPE) thyroid tissues obtained from patients belonging to intrathyroidal, invasive and metastatic thyroid carcinoma groups
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Project description:Paillary thyroid cancer (PTC) is the most common type of thyroid malignancy. Extrathyroidal invasion (ETİ), lymph node metastasis, and distance organ metastasis is poor prognostic factor in PTC. The metastasis is still a leading cause of papillary thyroid cancer death. The early detection of metastatic signature is crucial for identification of thyroid cancer prognosis and personalized therapeutic strategies. In the present study, we present thyroid cancer metastasis and invasivenes related miRNAs identified by comprehensive miRNA expression profiling of formalin-fixed paraffin embedded (FFPE) thyroid tissues obtained from patients belonging to intrathyroidal, invasive and metastatic thyroid carcinoma groups
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Project description:Label-free proteomics profiling of 37 paired tumor-normal tissues of papillary thyroid cancer
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Project description:Papillary thyroid cancers (PTC) that invade into local structures are associated with a poor prognosis, but the mechanisms for PTC invasion are incompletely defined limiting the development of new therapies. To characterize biological processes involved in PTC invasion, we analyzed the gene expression profiles of microscopically dissected intratumoral samples from central and invasive regions of seven widely invasive PTCs and normal thyroid tissue by oligonucleotide microarray and performed confirmatory expression and functional studies. In comparison to the central regions of primary PTCs, the invasive fronts overexpressed TGFbeta, NFkappaB and integrin pathway members, and regulators of small G-proteins and CDC42. Moreover, reduced levels of mRNAs encoding proteins involved in cell-cell adhesion and communication were identified, consistent with epithelial-to-mesenchymal transition (EMT). To confirm that aggressive PTCs were characterized by EMT, 35 additional PTCs were examined for expression of vimentin, a hallmark of EMT. Overexpression of vimentin was associated with PTC invasion and nodal metastasis. Functional, in vitro studies demonstrated that vimentin was required for the development and maintenance of both a mesenchymal morphology and invasiveness in thyroid cancer cells. We conclude that EMT is a common mechanism of PTC invasion and that vimentin regulates thyroid cancer EMT in vitro. Keywords: Genetic modification
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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.
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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
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Project description:Phosphorylated proteomics profiling were performed on 37 paired tumor-normal tissues of human papillary thyroid cancer
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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
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