MicroRNAs: uma ferramenta auxiliar na sub-classificação de tumores renais

Os tumores de células renais (TCR) são clinicamente, morfologicamente e geneticamente heterogéneos. A correcta identificação dos carcinomas de células renais (CCR), bem como a sua discriminação do tecido normal e dos tumores benignos é de extraordinária relevância clínica. Actualmente, sabe-se que os microRNAs podem apresentar diferentes níveis de expressão entre tecidos tumorais e normais, podendo auxiliar no diagnóstico de neoplasias, incluindo os TCRs. Com este trabalho verificou-se que os TCRs apresentam níveis de expressão dos miR-21, miR-141 e miR-200b significativamente mais baixos do que o tecido renal normal. De referir, ainda, que todos os miRs analisados apresentaram níveis de expressão significativamente diferentes entre TCRs malignos e benignos (oncocitomas). A análise da expressão de miR-141/miR-200b discriminou com elevada acuidade os TCRs dos tecidos renais normais, bem como dos oncocitomas. Adicionalmente, o nível de expressão deste painel de genes permitiu distinguir correctamente os TCR do tipo cromófobo dos oncocitomas. Foi ainda possível demonstrar que esta análise é exequível em biópsias aspirativas por agulha fina, podendo constituir um método auxiliar para o diagnóstico na rotina hospitalar.

Autores e afiliações:
Rui M. Silva-Santos1,2, Pedro Costa-Pinheiro1,2*, Ana Luís1,3*, Luís Antunes4, Francisco Lobo5, Jorge Oliveira5, Rui Henrique1,3,6, Carmen Jerónimo1,2,6*

1.Cancer Epigenetics Group, Research Center of the Portuguese Oncology Institute, Porto, Portugal; Departments of 2.Genetics, 3.Pathology, 4.Epidemiology and 5.Urology - Portuguese Oncology Institute, Porto, Portugal; 6.Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Portugal

*equal contribution

Abstract:
Renal cell tumors (RCT) are clinically, morphologically and genetically heterogeneous. Accurate identification of renal cell carcinomas (RCC) and its discrimination from normal tissue and benign tumors is mandatory. We, thus, aimed to define a panel of microRNAs that might aid in the diagnostic workup of RCTs. Fresh-frozen tissues from 120 RCTs (clear cell RCC, papillary RCC, chromophobe RCC and oncocytomas: 30 cases each), 10 normal renal tissues and 60 cases of ex vivo fine-needle aspiration biopsies from RCTs (15 of each subtype – validation set) were collected. Expression levels of miR-21, miR-141, miR-155, miR-183 and miR-200b were assessed by quantitative reverse transcription-PCR (qRT-PCR). Receiver Operator Characteristics (ROC) curves were constructed and the areas under the curve (AUC) were calculated to assess diagnostic performance. Disease-specific survival curves and a Cox regression model comprising all significant variables were computed. RCTs displayed significantly lower expression levels of miR-21, miR-141, and miR-200b compared to normal tissues and expression levels of all miRs differed significantly between malignant and benign RCTs. Expression analysis of miR-141/miR-200b accurately distinguished RCTs from normal renal tissues, oncocytoma from RCC and chromophobe RCC from oncocytoma. The diagnostic performance was confirmed in the validation set. Interestingly, miR-21, miR-141 and miR-155 expression levels showed prognostic significance, in univariate analysis. The miR-141/miR200b panel accurately distinguishes RCC from normal kidney and oncocytoma in tissue samples, discriminating from normal kidney and oncocytoma, whereas miR-21, miR-141 and miR-155 convey prognostic information. This approach is feasible in fine-needle aspiration biopsies and might provide an ancillary tool for routine diagnosis.

Revista:
British Journal of Cancer

Link:
http://www.ncbi.nlm.nih.gov/pubmed/24129247