RESUMO
The molecular determinants of thyroid follicular nodules are incompletely understood and assessment of malignancy is a diagnostic challenge. Since microRNA (miRNA) analyses could provide new leads to malignant progression, we characterised the global miRNA expression in follicular adenoma (FA) and follicular carcinoma (FC). Comparison of carcinoma and adenoma with normal thyroid revealed 150 and 107 differentially expressed miRNAs respectively. Most miRNAs were down-regulated and especially miR-199b-5p and miR-144 which were essentially lost in the carcinomas. Integration of the changed miRNAs with differentially expressed mRNAs demonstrated an enrichment of seed sites among up-regulated transcripts encoding proteins implicated in thyroid tumourigenesis. This was substantiated by the demonstration that pre-miR-199b reduced proliferation when added to cultured follicular thyroid carcinoma cells. The down-regulated miRNAs in FC exhibited a substantial similarity with down-regulated miRNAs in anaplastic carcinoma (AC) and by gene set enrichment analysis, we observed a significant identity between target mRNAs in FC and transcripts up-regulated in AC. To examine the diagnostic potential of miRNA expression pattern in distinguishing malignant from benign nodules we employed a supervised learning algorithm and leave-one-out-cross-validation. By this procedure, FA and FC were identified with a negative predicted value of 83% (data generated by microarray platform) and of 92% (data generated by qRT-PCR platform). We conclude that follicular neoplasia is associated with major changes in miRNA expression that may promote malignant transformation by increasing the expression of transcripts encoding tumourigenic factors. Moreover, miRNA profiling may facilitate the diagnosis of carcinoma vs adenoma.
Assuntos
Adenocarcinoma Folicular/genética , Transformação Celular Neoplásica/genética , Regulação para Baixo , MicroRNAs/genética , Neoplasias da Glândula Tireoide/genética , Adenocarcinoma Folicular/classificação , Adenocarcinoma Folicular/metabolismo , Adulto , Idoso , Linhagem Celular Tumoral , Proliferação de Células , Análise por Conglomerados , Biologia Computacional/métodos , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , RNA Mensageiro/metabolismo , Transdução de Sinais , Neoplasias da Glândula Tireoide/classificação , Neoplasias da Glândula Tireoide/metabolismoRESUMO
The treatment strategy for oral squamous cell carcinoma in Denmark has traditionally varied between the different head and neck oncology centres. A study group within the Danish Society for Head and Neck Oncology (DSHHO) was formed with the aim of optimising and standardising the treatment strategy. The approach was to use single modality treatment for stage I, stage II and some stage III and combined modality treatment for stage III and IV. Surgery was the preferred treatment when it was considered possible to perform a radical excision of the tumour and possible lymph node metastases with acceptable aesthetic and functional outcome. The implementation of a recognised national guideline facilitates prospective studies on a large well-characterised cohort. This increases the possibility of obtaining valid data on parameters such as morbidity, loco-regional control and survival. In addition the establishment of a reference program facilitates national monitoring of the treatment using defined indicators and standards.
