ABSTRACT
Sistemas de reparo do DNA, genes e proteínas, são essenciais para manutenção da integridade do genoma, evitando graves doenças como o câncer. Desrregulação na expressão destas proteínas vem sendo associado tanto ao risco do desenvolvimento, como na evolução de variados cânceres humanos com destaque para o carcinoma epidermoide oral. O objetivo deste trabalho foi analisar a imunoexpressão das proteínas de reparo do DNA, XRCC1, THIIF e XPF em carcinoma epidermoide de língua oral (CELO) e investigar associação com parâmetros clínicos, histopatológicos, de desfecho e sobrevida em cinco anos. Setenta e quatro casos de CELO foram analisados por meio da técnica da imuno-histoquímica de forma semiquantitativa. Observou-se alta expressão das proteínas pesquisadas nas células parenquimatosas, identificando associação significativa da elevada expressão de XRCC1 com melhor estadiamento clínico (p=0,02). A regressão de Cox revelou tamanho do tumor (p<0,01), comprometimento linfonodal (p=0,04), estágio do tumor (p=0,02) e profundidade de invasão >4mm (p=0,05) como fatores prognósticos para CELO. Os resultados deste experimento sugerem que as proteínas XRCC1, TFIIH e XPF participam do processo de tumorigênese, entretanto a imunoexpressão das mesmas não pode ser utilizada como indicador independente de prognóstico para CELO (AU).
DNA repair systems, genes and proteins are essential for genome integrity maintenance, avoiding serious diseases such as cancer. Deregulation in the expression of those proteins has been associated with both the risk of development and evolution of various human cancers, including oral squamous cell carcinoma. The purpose of this study was to analyze the immunoreactivity of the DNA repair proteins XRCC1, THIIF and XPF in oral tongue squamous cell carcinoma (OTSCC) and to investigate its association with clinical and histopathological parameters, outcome and 5-year survival rate. Seventy-four cases of OTSCC were analyzed semi-quantitatively through immunohistochemistry. We observed that DNA repair proteins were highly expressed in parenchymal cells; however, we only observed a significant association between XRCC1 high expression and better clinical staging (p=0,02). Cox regression showed that tumor size (p<0,01), lymph node involvement (p=0,04), tumor stage (p=0,02) and depth of invasion> 4mm (p=0,05) were prognostic factors. The results of this experiment suggest that XRCC1, TFIIH and XPF participate in the tumorigenic process, however, their immunoexpression may not be used as an independent prognostic indicator for OTSCC (AU).
Subject(s)
Humans , Male , Female , Child , Adolescent , Adult , Middle Aged , Aged , Carcinoma, Squamous Cell/pathology , DNA Repair , Transcription Factor TFIIH , X-ray Repair Cross Complementing Protein 1 , Immunohistochemistry/methods , Survival Analysis , Data Interpretation, Statistical , Longitudinal StudiesABSTRACT
El sistema de reparación del daño al DNA por escisión de nucleótidos (NER), es un sistema de reparación altamente versátil y sofisticado, que contrarresta los efectos deletéreos de las lesiones en el DNA, incluyendo la radiación ultravioleta...
Subject(s)
Humans , DNA , Skin Diseases, Genetic , Transcription Factor TFIIHABSTRACT
Xeroderma pigmentosum group D (XPD) gene is the second subunit of basic transcript factor TFII H; it plays an important role in transcription and nucleotide excision repair. In this study, using the total RNA extracted from HeLa cells, we cloned the human full length XPD by RT-PCR and inserted it into the pEGFP-N2 plasmid vector which expressed the green fluorescence protein (GFP). Then the recombinant plasmid pEGFP-N2/XPD was transfected into the human hepatoma carcinoma cell Hep3B integrated with HBx protein,and we analysed the expression of HBx and the proliferative ability of recombinant cells. The data collected from this study could serve as a physical basis on which to further investigate the biological activities of XPD.