Gene expression analysis reveals evidence for inactivation of the TGF-β signaling cascade in autonomously functioning thyroid nodules

Eszlinger, Markus; Krohn, Knut; Frenzel, R.; Kropf, Siegfried; Tönjes, Anke; Paschke, Ralf

doi:10.1038/sj.onc.1207186

Cited by 49 publications

(40 citation statements)

References 40 publications

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“…First, where the two microarray analyses overlap, their results are similar, even though different samples and different arrays and protocols for samples processing were used. Second, we confirmed several regulations already identified previously (Deleu et al, 2000;Eszlinger et al, 2001Eszlinger et al, , 2004O'Donovan et al, 2002;Finley et al, 2004;Mazzanti et al, 2004;Detours et al, 2005). Moreover, several findings are in line with data obtained in different but related systems such as thyroid cells or other cells chronically stimulated by the cAMP pathway (Yamazaki et al, 2003).…”

Section: Discussionsupporting

confidence: 91%

“…Decreased expression of several genes confirms previous data obtained in our group and by others: ApoD, myosin (Eszlinger et al, 2004), c-fos, fosB, junB, c-myc and TR3 (NGFIB) (Deleu et al, 2000). Several genes are downregulated in both analysis I and II, but only by a factor of less than 3 in analysis II, namely clusterin, bcd, ATF3, cav1, DUSP1, junB and TR3.…”

Section: General Survey Of Gene Expression (Analysis Ii)supporting

confidence: 90%

“…Quite a few upregulations confirm previously obtained data: thyroperoxidase (Deleu et al, 2000), deiodinase (dio1), sialylyltransferase, protein kinase C b , collagen IV and IX (Eszlinger et al, 2004). FcGBP has been shown to be upregulated in follicular adenomas (O'Donovan et al, 2002).…”

Section: General Survey Of Gene Expression (Analysis Ii)supporting

confidence: 83%

“…While several groups have reported gene expression profiles in follicular adenomas and in follicular and papillary carcinomas (Huang et al, 2001;Aldred et al, 2003;Barden et al, 2003;Yano et al, 2004), only one similar study has been performed so far (Eszlinger et al, 2004). Our data set provides considerable new information about proteins and pathways involved in this disease, which will now be the subject of more detailed investigations.…”

Section: Discussionmentioning

confidence: 81%

“…FcGBP has been shown to be upregulated in follicular adenomas (O'Donovan et al, 2002). Alcohol DH (Eszlinger et al, 2004) and solute carrier expressions are also increased in the Tg-A2aR mice thyroids, an animal model of autonomous adenomas (Goffard et al, 2004). Phosphodiesterase expression is classically increased in response to cAMP and PKA activation (Cho-Chung, 2004).…”

Section: General Survey Of Gene Expression (Analysis Ii)mentioning

confidence: 99%

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Gene expression in thyroid autonomous adenomas provides insight into their physiopathology

Wattel¹,

Mircescu²,

Venet³

et al. 2005

Oncogene

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The purpose of this study was to use the microarray technology to define expression profiles characteristic of thyroid autonomous adenomas and relate these findings to physiological mechanisms. Experiments were performed on a series of separated adenomas and their normal counterparts on Micromax cDNA microarrays covering 2400 genes (analysis I), and on a pool of adenomatous tissues and their corresponding normal counterparts using microarrays of 18 000 spots (analysis II). Results for genes present on the two arrays corroborated and several gene regulations previously determined by Northern blotting or microarrays in similar lesions were confirmed. Five overexpressed and 24 underexpressed genes were also confirmed by real-time RT-PCR in some of the samples used for microarray analysis, and in additional tumor specimens. Our results show: (1) a change in the cell populations of the tumor, with a marked decrease in lymphocytes and blood cells and an increase in endothelial cells. The latter increase would correspond to the establishment of a close relation between thyrocytes and endothelial cells and is related to increased N-cadherin expression. It explains the increased blood flow in the tumor; (2) a homogeneity of tumor samples correlating with their common physiopathological mechanism: the constitutive activation of the thyrotropin (TSH)/cAMP cascade; (3) a low proportion of regulated genes consistent with the concept of a minimal deviation tumor; (4) a higher expression of genes coding for specific functional proteins, consistent with the functional hyperactivity of the tumors; (5) an increase of phosphodiesterase gene expression which explains the relatively low cyclic AMP levels measured in these tumors; (6) an overexpression of antiapoptotic genes and underexpression of proapoptotic genes compatible with their low apoptosis rate; (7) an overexpression of N-cadherin and downregulation of caveolins, which casts doubt about the use of these expressions as markers for malignancy.Oncogene (2005) 24, 6902-6916.

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Section: Discussionsupporting

confidence: 91%

Section: General Survey Of Gene Expression (Analysis Ii)supporting

confidence: 90%

Section: General Survey Of Gene Expression (Analysis Ii)supporting

confidence: 83%

Section: Discussionmentioning

confidence: 81%

Section: General Survey Of Gene Expression (Analysis Ii)mentioning

confidence: 99%

See 3 more Smart Citations

Gene expression in thyroid autonomous adenomas provides insight into their physiopathology

Wattel¹,

Mircescu²,

Venet³

et al. 2005

Oncogene

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Comparison of Independent Samples of High‐Dimensional Data by Pairwise Distance Measures

et al. 2007

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Pairwise distance or association measures of sample elements are often used as a basis for hierarchical cluster analyses. They can also be used in tests for the comparison of pre-defined subgroups of the total sample. Usually this is done with permutation tests In this paper, we compare such a procedure with alternative tests for high-dimensional data based on spherically distributed scores in simulation experiments and with real data. The tests based on the pairwise distance or similarity measures perform quite well in this comparison. As the number of possible permutations is small in very small samples, this might restrict the use of the test. Therefore, we propose an exact parametric small sample version of the test using randomly rotated samples.

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Contemporary diagnostic approach to the thyroid nodule

Rosen

Stone

2006

Journal of Surgical Oncology

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Thyroid nodules are common, with an estimated incidence of 5%-10% in the United States. The current gold standard for diagnosis is fine needle aspiration biopsy (FNAB). The incidence of indeterminate diagnoses varies from 10% to 25%. Surgical resection is usually indicated to exclude the diagnosis of cancer in these patients. However, only a minority (about 20%) of indeterminate thyroid nodules actually harbor a malignancy, resulting in surgery for diagnostic purposes alone in many patients. The increased detection of benign nodules and microcarcinomas reinforces the need for improved non-operative methods to differentiate benign from malignant disease and discriminate low-risk from high-risk cancers. In this article we present a current, rational diagnostic approach to the patient with a thyroid nodule, evaluate new advances including thyroid genomic and predictor models, and propose the development of prospective trials to incorporate these new additions into clinical decision making. Given how many questions still exist for patients with thyroid nodules, partnership and collaboration, or the "bench to bedside" concept should find its way into most every thyroid surgeon and endocrinologist's lexicon.

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Gene expression analysis reveals evidence for inactivation of the TGF-β signaling cascade in autonomously functioning thyroid nodules

Cited by 49 publications

References 40 publications

Gene expression in thyroid autonomous adenomas provides insight into their physiopathology

Gene expression in thyroid autonomous adenomas provides insight into their physiopathology

Comparison of Independent Samples of High‐Dimensional Data by Pairwise Distance Measures

Contemporary diagnostic approach to the thyroid nodule

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