Assuntos
Carcinoma Basocelular/genética , Regulação Neoplásica da Expressão Gênica , Fatores de Transcrição SOX9/genética , Neoplasias Cutâneas/genética , Fatores de Transcrição da Família Snail/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Basocelular/patologia , Linhagem Celular Tumoral , Regulação para Baixo , Transição Epitelial-Mesenquimal/genética , Feminino , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/patologia , RNA Mensageiro/metabolismo , Pele/patologia , Neoplasias Cutâneas/patologia , Regulação para CimaRESUMO
Purpose. Melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) can be used as a unique model to identify molecular mechanisms to distinguish rarely metastatic (BCC), often metastatic (SCC) and most metastatic (melanoma) cancer. It is known that epithelial-mesenchymal transition and stemness transcription factors (TWIST1, SNAI2/SLUG, and BMI1) play an important role in metastasis and their dysregulation has been demonstrated in metastatic cancers. We hypothesized that this spectrum of cutaneous cancers (BCC, SCC, and melanoma) would be a unique cancer model system to elucidate steps toward cancer invasion and metastasis. Methods. We evaluated the mRNA expression level of BMI1, TWIST1, and SNAI2/SLUG and studied clinicopathological features in 170 skin cancers along with normal tissue samples. Results. We demonstrate downregulation of BMI1 mRNA expression in BCC samples compared with controls (p = 0.0001), SCC (p = 0.001), and melanoma (p = 0.0001) samples. Downregulation of TWIST1 mRNA expression is seen in only BCC samples compared with controls (p = 0.031). High SNAI2 mRNA expression is represented in melanoma samples compared with controls (p = 0.022) and SCC samples (p = 0.031). High mRNA expression of TWIST1 is seen in patients with positive history of cancers. Extremely low mRNA expression of BMI1 is detected in patients with positive history of cancers other than skin cancer. Conclusions. These findings provide support for the hypothesis that the spectrum of cutaneous cancers could be better understood as a series of gene dosage-dependent entities with distinct molecular events. Oncogene-induced senescence, mechanism of which is still unclear, could be one explanation for these results (AU)
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Assuntos
Humanos , Masculino , Feminino , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Regulação Neoplásica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/genética , Melanoma/diagnóstico , Neoplasia de Células Basais/complicações , Neoplasia de Células Basais/diagnóstico , Expressão Gênica , Expressão Gênica/genética , RNA Mensageiro/genética , Metástase Neoplásica/diagnóstico , Reação em Cadeia da Polimerase/métodos , Análise de Variância , Curva ROCRESUMO
PURPOSE: Melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) can be used as a unique model to identify molecular mechanisms to distinguish rarely metastatic (BCC), often metastatic (SCC) and most metastatic (melanoma) cancer. It is known that epithelial-mesenchymal transition and stemness transcription factors (TWIST1, SNAI2/SLUG, and BMI1) play an important role in metastasis and their dysregulation has been demonstrated in metastatic cancers. We hypothesized that this spectrum of cutaneous cancers (BCC, SCC, and melanoma) would be a unique cancer model system to elucidate steps toward cancer invasion and metastasis. METHODS: We evaluated the mRNA expression level of BMI1, TWIST1, and SNAI2/SLUG and studied clinicopathological features in 170 skin cancers along with normal tissue samples. RESULTS: We demonstrate downregulation of BMI1 mRNA expression in BCC samples compared with controls (p = 0.0001), SCC (p = 0.001), and melanoma (p = 0.0001) samples. Downregulation of TWIST1 mRNA expression is seen in only BCC samples compared with controls (p = 0.031). High SNAI2 mRNA expression is represented in melanoma samples compared with controls (p = 0.022) and SCC samples (p = 0.031). High mRNA expression of TWIST1 is seen in patients with positive history of cancers. Extremely low mRNA expression of BMI1 is detected in patients with positive history of cancers other than skin cancer. CONCLUSIONS: These findings provide support for the hypothesis that the spectrum of cutaneous cancers could be better understood as a series of gene dosage-dependent entities with distinct molecular events. Oncogene-induced senescence, mechanism of which is still unclear, could be one explanation for these results.
