Gene expression profilling of anaplastic thyroid carcinomas (ATC) and normal thyroid tissues
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE53072 | GEO | 2013/12/07
SECONDARY ACCESSION(S): PRJNA230799
REPOSITORIES: GEO
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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:The E3 SUMO ligase PIAS2 is expressed at high levels in differentiated papillary thyroid carcinomas but at low levels in anaplastic thyroid carcinomas (ATC), an undifferentiated cancer with very high mortality. Double-stranded RNA–directed RNA interference (dsRNAi) targeting the PIAS2 isoform beta (PIAS2b) inhibits growth of ATC cell lines and patient primary cultures in vitro and orthotopic patient-derived xenografts (oPDX) in vivo, but not of thyroid cell lines or non-anaplastic primary thyroid cultures (differentiated carcinoma, benign lesions, or normal). PIAS2b-dsRNAi also has an anti-cancer effect on other anaplastic human cancers (pancreas, lung, and gastric). Mechanistically, PIAS2b is required for proper mitotic spindle and centrosome assembly, and it is a dosage-sensitive protein in ATC. Strikingly, PIAS2b-dsRNAi induces mitotic catastrophe at prophase. High-throughput proteomics revealed the proteasome (PSMC5) and spindle cytoskeleton as direct targets of PIAS2b SUMOylation at mitotic initiation. PIAS2b-dsRNAi is a promising therapy for ATC and other aggressive anaplastic cancers.
2024-04-08 | PXD044110 | Pride
Project description:Anaplastic thyroid carcinoma (ATC) is the most fatal and rapidly evolving endocrine malignancy invading the head and neck region and accounting for the majority of thyroid cancer-associated deaths. Deregulation of microRNA (miRNA) expression promotes thyroid carcinoma progression by modulating reorganization of the ATC transcriptome. Here, we applied comparative miRNA-/mRNA-sequencing in a cohort of 28 thyroid carcinomas to unravel the association of deregulated miRNA and mRNA expression. This identifies 85 miRNAs significantly deregulated in ATC. By establishing a new analysis pipeline we unravel 85 prime miRNA-mRNA interactions supporting the downregulation of candidate tumor-suppressors and upregulation of bona fide oncogenes like survivin (BIRC5) in ATC. This miRNA-dependent reprogramming of the ATC transcriptome provides a mRNA signature comprising 65 genes sharply distinguishing ATC from other thyroid carcinomas. Validation of deregulated protein expression in an independent thyroid carcinoma cohort demonstrates that miRNA-dependent oncogenes comprised in this signature, the transferrin receptor TFRC (CD71) and the E3-ubiquitin ligase DTL, are sharply upregulated in ATC. This upregulation is even sufficient to distinguish ATC from partially differentiated thyroid carcinomas (PDTC). In sum, these findings provide new diagnostic tools and a robust resource to explore key miRNA-mRNA regulation underlying the progression of thyroid carcinoma.
2021-11-23 | GSE185719 | GEO
Project description:We profiled the gene expression of 11 anaplastic thyroid carcinomas (ATC), 49 papillary thyroid carcinomas (PTC) and 45 normal thyroids (N)
2012-11-09 | GSE33630 | GEO
Project description:We profiled the gene expression of 11 anaplastic thyroid carcinomas (ATC), 49 papillary thyroid carcinomas (PTC) and 45 normal thyroids (N) We hibridized a series of anaplastic thyroid carcinomas (ATC) and papillary thyroid carcinomas (PTC) onto Affymetrix U133 Plus 2.0 arrays. ATCs were obtained from different hospitals in France and Belgium. Paired RNA samples of PTCs and non-tumoral thyroid tissues were obtained from Ukraine via the Chernobyl Tissue Bank (www.chernobyltissuebank.com). Diagnoses were confirmed by the members of the International Pathology Panel of the Chernobyl Tissue Bank.
2012-11-09 | E-GEOD-33630 | biostudies-arrayexpress
Project description:Currently there is a lack of effective therapies which result in long-term durable response for patients presenting with anaplastic thyroid carcinoma (ATC), a very rare and lethal variant of thyroid cancer. ATC is resistant to chemotherapy, radiation, and targeted therapies currently available. In an effort to identify novel tumor-specific therapeutic targets, we performed high throughput gene array analysis screening numerous ATC cell lines, and compared their gene expression levels to normal thyroid cell lines.
2016-11-30 | GSE85457 | GEO
Project description:Currently there is a lack of effective therapies which result in long-term durable response for patients presenting with anaplastic thyroid carcinoma (ATC), a very rare and lethal variant of thyroid cancer. ATC is resistant to chemotherapy, radiation, and targeted therapies currently available. In an effort to identify novel tumor-specific therapeutic targets, we performed high throughput gene array analysis screening numerous patient ATC tumor tissues, and compared their gene expression levels to matched and unmatched normal thyroid tissue samples.
2015-01-22 | GSE65144 | GEO
Project description:Currently there is a lack of effective therapies which result in long-term durable response for patients presenting with anaplastic thyroid carcinoma (ATC), a very rare and lethal variant of thyroid cancer. ATC is resistant to chemotherapy, radiation, and targeted therapies currently available. In an effort to identify novel tumor-specific therapeutic targets, we performed high throughput gene array analysis screening numerous patient ATC tumor tissues, and compared their gene expression levels to matched and unmatched normal thyroid tissue samples. RNA was extracted from flash frozen patient tumor and normal samples. Gene array analysis was performed, and resulting expression levels were compared between normal and tumor samples.
2015-01-22 | E-GEOD-65144 | biostudies-arrayexpress
Project description:Anaplastic thyroid carcinomas (ATC) are rare, but represent the most lethal malignancy of the thyroid. Selective molecular markers and drivers distinguishing ATC from other thyroid carcinomas of follicular origin remain largely unknown, limiting advances in diagnosis and treatment. In a retrospective study, we analyzed gene expression in 36 ATC, 18 poorly-differentiated, 132 papillary and 55 follicular thyroid carcinoma, as well as 124 paired and un-paired normal thyroid tissues in three independent cohorts by RNA-sequencing and immunohistochemistry. RNA-sequencing data in the test cohort suggested selective ATC protein biomarkers. Evaluation of these revealed that ATCs are characterized by the de novo expression of various testis antigens, including melanoma-associated antigen A3 (MAGEA3), but most importantly the oncofetal IGF2 mRNA binding protein 1 (IGF2BP1). Shallow whole genome-sequencing essentially excluded, that IGF2BP1 upregulation results from gene copy number alterations. Immunohistochemical analyses in all three tumor cohorts confirmed selective de novo expression of IGF2BP1 protein in ATC. In sum, 75 % (27/36) of all tested ATC and 0.5 % (1/204) of poorly and well-differentiated thyroid carcinoma tissue samples were positive for IGF2BP1 protein. This indicates that IGF2BP1 protein expression identifies ATC with a diagnostic odds ratio of 612 (95 % CI: 74.6 to 5021). In addition, we found that MAGEA3 is exclusively, although less consistently upregulated in ATC, presenting with an odds ratio of 411 (95 % CI: 23.8 to 7098.7). Importantly, we provide confirmatory evidence that IGF2BP1 and MAGEA3 expression distinguishes ATC from partially differentiated thyroid carcinomas (PDTCs). IGF2BP1 furthermore identified ATC foci within low-grade follicular thyroid carcinoma. In conclusion, IGF2BP1 represents the most promising single-gene marker available for ATC, followed by MAGEA3, improving on current techniques. Robust markers are essential to help distinguish this high-grade malignancy from other thyroid carcinomas, to guide surgical decision making, therapy and post-resection/therapy monitoring strategies.
2020-07-07 | GSE126728 | GEO
Project description:Anaplastic thyroid carcinomas (ATC) are rare, but represent the most lethal malignancy of the thyroid. Selective molecular markers and drivers distinguishing ATC from other thyroid carcinomas of follicular origin remain largely unknown, limiting advances in diagnosis and treatment. In a retrospective study, we analyzed gene expression in 36 ATC, 18 poorly-differentiated, 132 papillary and 55 follicular thyroid carcinoma, as well as 124 paired and un-paired normal thyroid tissues in three independent cohorts by RNA-sequencing and immunohistochemistry. RNA-sequencing data in the test cohort suggested selective ATC protein biomarkers. Evaluation of these revealed that ATCs are characterized by the de novo expression of various testis antigens, including melanoma-associated antigen A3 (MAGEA3), but most importantly the oncofetal IGF2 mRNA binding protein 1 (IGF2BP1). Shallow whole genome-sequencing essentially excluded, that IGF2BP1 upregulation results from gene copy number alterations. Immunohistochemical analyses in all three tumor cohorts confirmed selective de novo expression of IGF2BP1 protein in ATC. In sum, 75 % (27/36) of all tested ATC and 0.5 % (1/204) of poorly and well-differentiated thyroid carcinoma tissue samples were positive for IGF2BP1 protein. This indicates that IGF2BP1 protein expression identifies ATC with a diagnostic odds ratio of 612 (95 % CI: 74.6 to 5021). In addition, we found that MAGEA3 is exclusively, although less consistently upregulated in ATC, presenting with an odds ratio of 411 (95 % CI: 23.8 to 7098.7). Importantly, we provide confirmatory evidence that IGF2BP1 and MAGEA3 expression distinguishes ATC from partially differentiated thyroid carcinomas (PDTCs). IGF2BP1 furthermore identified ATC foci within low-grade follicular thyroid carcinoma. In conclusion, IGF2BP1 represents the most promising single-gene marker available for ATC, followed by MAGEA3, improving on current techniques. Robust markers are essential to help distinguish this high-grade malignancy from other thyroid carcinomas, to guide surgical decision making, therapy and post-resection/therapy monitoring strategies.
2020-07-07 | GSE126698 | GEO