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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

High Diagnostic Accuracy Based on CLDN10, HMGA2, and LAMB3 Transcripts in Papillary Thyroid Carcinoma

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Autor(es):
Barros-Filho, Mateus Camargo [1] ; Marchi, Fabio Albuquerque [1] ; Pinto, Clovis Antonio [1] ; Rogatto, Silvia Regina [1, 2] ; Kowalski, Luiz Paulo [1]
Número total de Autores: 5
Afiliação do(s) autor(es):
[1] AC Camargo Canc Ctr, Int Res Ctr, BR-01509010 Sao Paulo, SP - Brazil
[2] Sao Paulo State Univ, Fac Med, BR-18618970 Botucatu, SP - Brazil
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM; v. 100, n. 6, p. E890-E899, JUN 2015.
Citações Web of Science: 25
Resumo

Context: Thyroid nodules are common in adult population and papillary thyroid carcinoma (PTC) is the most frequent malignant finding. The natural history of PTC remains poorly understood and current diagnostic methods limitations are responsible for a significant number of potentially avoidable surgeries. Objective: This study aimed to identify molecular markers to improve the diagnosis of thyroid lesions. Design: Gene expression profiling was performed using microarray in 61 PTC and 13 surrounding normal tissues (NT). A reliable gene list was established using cross-study validation (138 matched PTC/NT from external databases). Results were collectively interpreted by in silico analysis. A panel of 28 transcripts was evaluated by RT-qPCR, including benign thyroid lesions (BTL) and other follicular cell-derived thyroid carcinomas (OFDTC). Adiagnostic algorithm was developed (training set: 23 NT, 8 BTL, and 86 PTC), validated (independent set: 10 NT, 140 BTL, 120 PTC, and 12 OFDTC) and associated with clinical features. Results: GABRB2 was ranked as the most frequently up-regulated gene in PTC (cross-study validation). Altered genes in PTC suggested a loss of T-4 responsiveness and dysregulation of retinoic acid metabolism, highlighting the putative activation of EZH2 and histone deacetylases (predicted in silico). An algorithm combining CLDN10, HMGA2, and LAMB3 transcripts was able to discriminate tumors from BTL samples (94% sensitivity and 96% specificity in validation set). High algorithm scores were associated with regional lymph node metastases. Conclusions: A promising tool with high performance for PTC diagnosis based on three transcripts was designed with the potential to predict lymph node metastasis risk. (AU)

Processo FAPESP: 08/57887-9 - Instituto Nacional de Oncogenômica
Beneficiário:Luiz Paulo Kowalski
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 10/18370-0 - Análise de expressão gênica em larga escala do processo de extensão extra-tireoidiana e busca de algoritmos de predição de recidiva em pacientes com carcinoma papilífero de tireóide tratados com cirurgia e radioiodoterapia
Beneficiário:Luiz Paulo Kowalski
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 10/09526-7 - Expressão gênica global em carcinomas papilíferos de tireoide: busca de marcadores diagnósticos, prognósticos e alvos terapêuticos
Beneficiário:Mateus de Camargo Barros Filho
Linha de fomento: Bolsas no Brasil - Doutorado