Gene Expression Profiles Reveal that DCN, DIO1, and DIO2 Are Underexpressed in Benign and Malignant Thyroid Tumors

Abstract

To investigate the molecular events involved in the pathogenesis and/or progression of thyroid tumors, we compared the gene expression profiles of three thyroid carcinoma cell lines, which represent major tumor subtypes of thyroid cancer and normal thyroid tissue. Using cDNA array methodology, we investigated the expression of 1807 open reading frame expressed sequence tags (ORESTES), selected from head and neck tumor libraries generated through the Brazilian Human Cancer Project-LICR/FAPESP. We found that 505 transcripts were differentially expressed in the thyroid carcinoma cell lines. Using a more stringent criterion, transcripts underexpressed or overexpressed more than fivefold in 1 of 3 or 3 of 3 carcinoma cell lines, a list of 55 ESTs were detected. Five candidate genes were further validated by quantitative polymerase chain reaction (qPCR) in an independent set of 52 thyroid tumors and 22 matched normal thyroid tissues. DCN was found underexpressed in a high percentage of the follicular thyroid adenomas, follicular thyroid carcinomas, and follicular variant of papillary thyroid carcinomas. DIO1 and DIO2 were underexpressed in nearly all papillary thyroid carcinomas. These genes not only could help to better define a tumor signature for thyroid tumors, but may, in part, also become useful as potential targets for thyroid tumor treatment.

Metastatic Follicular Thyroid Carcinoma as a Cause of Low Serum Thyroxine with a Normal Thyroid Stimulating Hormone Level

“…In contrast, a high level of D2 activity has been reported in metastatic follicular thyroid carcinoma, resulting in an increased fractional conversion of T4 to T3. [2][3][4] D1 and D2 activities were assayed in the tumor resected from a patient in a previous case report. 2 The tumor D2 converted 73 ± 3% of T4 to T3, compared to 26 ± 3% in the normal human thyroid.…”

Nódulos com diagnóstico de padrão folicular: marcadores biológicos são o futuro?

“…Entre os genes identificados, 5 foram selecionados para validação em diferentes subtipos de tumores da tiróide. A validação dos achados mostrou que os marcadores eram diferencialmente expressos nos diferentes subtipos tumorais e podem contribuir para a compreensão da patogênese dos tumores da tiróide, não eram eficientes para serem utilizados como marcadores de diagnóstico (57).…”

“…re-avaliaram as listas resultantes de 21 estudos publicados (63). Neste trabalho foram incluídos dois trabalhos publicados pelo nosso grupo e que utilizaram metodologias "hightroughput" (57,62 sugerem que estes genes candidatos poderão auxiliar no desenvolvimento de um painel de marcadores que terá suficiente sensibilidade e especificidade para diagnóstico dos tumores da tiróide. Uma análise utilizando estes marcadores em material obtido da PAAF é necessária para rejeitar ou aceitar tal hipótese.…”

Type 2 iodothyronine deiodinase is highly expressed in medullary thyroid carcinoma

“…D2 plays a critical role in providing local T3 to regulate intracellular T3 concentration and recent studies suggest that this enzyme also contributes to a significant fraction of plasma T3 in rodents and humans Streckfuss et al, 2005). D2 is expressed in normal and stimulated human thyroid gland and has been evaluated as a possible marker of thyroid follicular cell differentiation (Arnaldi et al, 2005;De Souza Meyer et al, 2005;Kim et al, 2003;Murakami et al, 2001a;Salvatore et al, 1996;Takano et al, 2006). Previous studies have described underexpression of D2 in papillary thyroid carcinoma (PTC) (Arnaldi et al, 2005;Murakami et al, 2001a;).…”

“…D2 is expressed in normal and stimulated human thyroid gland and has been evaluated as a possible marker of thyroid follicular cell differentiation (Arnaldi et al, 2005;De Souza Meyer et al, 2005;Kim et al, 2003;Murakami et al, 2001a;Salvatore et al, 1996;Takano et al, 2006). Previous studies have described underexpression of D2 in papillary thyroid carcinoma (PTC) (Arnaldi et al, 2005;Murakami et al, 2001a;). In contrast, D2 are reported to be significant increased in follicular carcinoma (De Souza Meyer et al, 2005;Kim et al, 2003;Takano et al, 2006).…”