RESUMEN
BACKGROUND: The re-expression of pluripotent markers (Oct-4 and Nanog) and the reactivation of stem cell-related pathways in oral carcinoma have been well researched. However, the relationship between the stem cell signaling molecule ß-catenin and pluripotent markers Oct-4 and Nanog in oral cancer is yet to be studied in detail. Therefore, we have investigated the correlation among Oct-4, Nanog, and ß-catenin in oral squamous cell carcinoma, which, in turn, could provide valuable insight into its prognostic significance. METHODS: The immunohistochemical analysis was performed for 60 cases of oral cancer to study the expression pattern of Oct-4, Nanog, and ß-catenin. Whereas immunofluorescence analysis was used to investigate the co-localization of ß-catenin with Oct-4 and Nanog in oral carcinoma tissues and H314 cell line. Finally, co-immunoprecipitation analysis was used to study the possible interaction between ß-catenin and Oct-4 in oral carcinoma cells. RESULTS: ß-catenin, Oct-4, and Nanog showed significant correlation with lymph node metastasis, stage, grade, and prognosis in oral squamous cell carcinoma. Interestingly, a significant positive correlation was found among the expression of Oct-4, Nanog, and ß-catenin. Moreover, the interaction between ß-catenin and Oct-4 was observed in oral cancer. CONCLUSION: The positive correlation among Oct-4, Nanog, and ß-catenin suggests their coordinated role in maintaining proliferation in oral carcinoma cells. The interaction between ß-catenin and Oct-4 may be a crucial event in oral carcinogenesis. On the other hand, ß-catenin, Oct-4, and Nanog could be used as independent prognostic markers of oral squamous cell carcinoma.
Asunto(s)
Carcinoma de Células Escamosas/metabolismo , Neoplasias de Cabeza y Cuello/metabolismo , Proteínas de Homeodominio/metabolismo , Neoplasias de la Boca/metabolismo , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , beta Catenina/metabolismo , Anciano , Western Blotting , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Femenino , Técnica del Anticuerpo Fluorescente , Neoplasias de Cabeza y Cuello/patología , Humanos , Inmunohistoquímica , Inmunoprecipitación , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/patología , Proteína Homeótica Nanog , Pronóstico , Carcinoma de Células Escamosas de Cabeza y Cuello , Análisis de SupervivenciaRESUMEN
BACKGROUND: Besides the tissue-specific stem cell markers, neural and hematopoietic stem cell markers were found to play an important role in carcinogenesis. Based on this background, we have investigated the expression pattern and prognostic significance of neural stem cell markers, Nestin and Musashi-1, in oral cancer. METHODS: We used immunohistochemistry and immunofluorescence analyses to study the expression pattern and correlation between Nestin and Musashi-1 in oral squamous cell carcinoma. The Kaplan-Meier method was used to construct overall and disease-free survival curves, and the differences were calculated using log-rank test. RESULTS: Nestin expression was gradually increased in the transformation stages of oral cancer. Both Nestin and Musashi-1 expressions were associated with higher stage and poorly differentiated status of oral carcinoma. Interestingly, Nestin and Musashi-1 double positive cases showed statistically highly significant correlation with poorer survival of oral carcinoma patients. CONCLUSIONS: Expression of Nestin in the preneoplastic lesions indicates its role in the transformation of oral squamous epithelium. Clinicopathological and survival analyses suggest that Nestin and Musashi-1 might be associated with invasion, differentiation and poorer survival in oral squamous cell carcinoma. In addition to their role as independent prognostic indicators, Nestin and Musashi-1 double positivity can be used to select high-risk cases for effective therapy and this is the novel finding of this study. CLINICAL RELEVANCE: Nestin and Musashi-1 are found to be independent prognostic markers of oral cancer, and they might be used as molecular targets for effective therapy.
Asunto(s)
Carcinoma de Células Escamosas/metabolismo , Neoplasias de la Boca/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Nestina/metabolismo , Lesiones Precancerosas/metabolismo , Proteínas de Unión al ARN/metabolismo , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/patología , Transformación Celular Neoplásica , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Inmunohistoquímica , Masculino , Neoplasias de la Boca/patología , Estadificación de Neoplasias , Lesiones Precancerosas/patología , Pronóstico , Tasa de SupervivenciaRESUMEN
The present study focuses on the correlation between the expression pattern of ß-catenin (component of Wnt signaling), ΔNp63 (proliferation marker), and Notch 1 (transmembrane receptor) in oral squamous cell carcinoma. The study also aims to investigate the interaction between ß-catenin and ΔNp63 in oral cancer. Furthermore, we also analyzed the prognostic significance of ß-catenin, ΔNp63, and Notch 1 in oral squamous cell carcinoma. Immunohistochemical analysis of ß-catenin, ΔNp63, and Notch 1 were done in 62 cases of oral squamous cell carcinoma. Co-immunoprecipitation analysis was done to study the possible interaction between ß-catenin and ΔNp63 in oral cancer. Kaplan-Meier method was used to estimate overall and disease-free survival, and the Log-rank test was used to compare the resulting curves. Statistically significant positive correlation was found between the localization of ß-catenin and the expression of ΔNp63 (p = 0.001**, r (s) = 0.427), whereas, no significant association was found between the expression pattern of ß-catenin and Notch 1. Interestingly, interaction between ß-catenin and ΔNp63 was observed in oral carcinoma. Moreover, ß-catenin and ΔNp63 may be related to worst survival in oral carcinoma. Statistically significant positive association between localization of ß-catenin and expression of ΔNp63 suggests that they might have dependent roles in maintaining the proliferation of oral carcinoma cells. In addition, the downregulated expression of Notch 1 was related to invasion and differentiation status of oral carcinoma cells. Furthermore, ß-catenin and ΔNp63 may be used as independent prognostic markers of oral carcinoma. On the other hand, interaction of ß-catenin with ΔNp63 may be a key event in maintaining the proliferation of oral carcinoma cells. The present study indicates that ß-catenin and ΔNp63 may be used as independent prognostic markers of oral carcinoma and the interaction of ß-catenin with ΔNp63 may be a crucial event in regulating proliferation and differentiation of oral carcinoma cells, which may be used as a target for therapeutic implications.
Asunto(s)
Carcinoma de Células Escamosas/patología , Neoplasias de la Boca/patología , Receptor Notch1/análisis , Factores de Transcripción/análisis , Proteínas Supresoras de Tumor/análisis , beta Catenina/análisis , Adulto , Anciano , Biomarcadores de Tumor/análisis , Carcinoma de Células Escamosas/secundario , Diferenciación Celular , Línea Celular Tumoral , Proliferación Celular , Supervivencia sin Enfermedad , Regulación hacia Abajo , Femenino , Estudios de Seguimiento , Glucógeno Sintasa Quinasa 3/análisis , Glucógeno Sintasa Quinasa 3 beta , Humanos , Inmunoprecipitación , Queratina-14/análisis , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Invasividad Neoplásica , Estadificación de Neoplasias , Pronóstico , Fumar , Tasa de Supervivencia , Tabaco sin HumoRESUMEN
BACKGROUND: The present study focuses on the expression pattern of the stem cell markers CD133 and Musashi-1 in precancerous and cancerous tissues of oral epithelium. The study also aims to investigate the correlation of CD133 and Musashi-1 expression with clinicopathological factors. METHODS: Immunohistochemical analysis was done to investigate the expression pattern of CD133 and Musashi-1, whereas, the coexpression of CD133 and Musashi-1 was studied using immunofluorescence analysis. RESULTS: A gradual increase in the expression of CD133 and Musashi-1 was observed from normal to dysplasia to carcinoma. In addition, the expression of CD133 and Musashi-1 shows significant difference between the stages and histological types of oral carcinoma. Interestingly, coexpression of CD133 and Musashi-1 was observed in oral carcinoma and CAL27 cells. CONCLUSIONS: A gradual increase in the expression of CD133 and Musashi-1 from normal to dysplasia to carcinoma suggests the possible involvement of these 2 proteins in oral carcinogenesis. The overexpression of CD133 and Musashi-1 in advanced stages and also in poorly differentiated tumors reveals their relationship with invasion and differentiation status of oral carcinoma cells. Moreover, the significant positive correlation between CD133 and Musashi-1 expression suggests that they might have a functional relationship in oral carcinoma cells, which needs further investigation.