RESUMO
An important objective in nowadays research is the discovery of new biomarkers that can detect colon tumours in early stages and indicate with accuracy the status of the disease. The aim of our study was to identify potential biomarkers for colon cancer onset and progression. We assessed gene expression profiles of a list of 10 candidate genes (MMP-1, MMP-3, MMP-7, DEFA 1, DEFA-5, DEFA-6, IL-8, CXCL-1, SPP-1, CTHRC-1) by quantitative real time PCR in triplets of colonic mucosa (normal, adenoma, tumoral tissue) collected from the same patient during surgery for a group of 20 patients. Additionally we performed immunohistochemistry for DEFA1-3 and SPP1. We remarked that DEFA5 and DEFA6 are key factors in adenoma formation (p<0.05). MMP7 is important in the transition from a benign to a malignant status (p <0.01) and further in metastasis being a prognostic indicator for tumor transformation and for the metastatic potential of cancer cells. IL8, irrespective of tumor stage, has a high mRNA level in adenocarcinoma (p< 0.05). The level of expression for SPP1 is correlated with tumor level. We suggest that high levels of DEFAS, DEFA6 (key elements in adenoma formation), MMP7 (marker of colon cancer onset and progression to metastasis), SPP1 (marker of progression) and IL8 could be used to diagnose an early stage colon cancer and to evaluate the prognostic of progression for colon tumors. Further, if DEFA5 and DEFA6 level of expression are low but MMP7, SPP1 and IL8 level are high we could point out that the transition from adenoma to adenocarcinoma had already occurred. Thus, DEFA5, DEFA6, MMP7, IL8 and SPP1 consist in a valuable panel of biomarkers, whose detection can be used in early detection and progressive disease and also in prognostic of colon cancer.
Assuntos
Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Neoplasias do Colo/química , Neoplasias do Colo/genética , Idoso , Transformação Celular Neoplásica/genética , Neoplasias do Colo/enzimologia , Neoplasias do Colo/patologia , Proteína DEFICIENS/análise , Proteína DEFICIENS/genética , Progressão da Doença , Detecção Precoce de Câncer , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Interleucina-8/análise , Interleucina-8/genética , Masculino , Metaloproteinase 7 da Matriz/análise , Metaloproteinase 7 da Matriz/genética , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Osteopontina/análise , Osteopontina/genética , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Prognóstico , RNA Mensageiro/análise , Sensibilidade e EspecificidadeRESUMO
Diethylstilbestrol (DES) was prescribed for almost 30 years by physicians who believed the nonsteroidal synthetic estrogen was beneficial in both the treatment of threatened abortions and the prevention of spontaneous abortions. Toxemia, premature delivery, postmaturity, and stillbirth were said to be significantly reduced in patients who were treated with DES. The consequences of in utero exposure to DES on female progeny have been widely publicized. However, male progeny also suffer the effects of in utero exposure to DES. These effects include epididymal cysts, small penile size, and cryptorchidism. Altered reproductive capacity is suggested by diminished sperm counts and sperm penetration assays.
