RESUMEN
BACKGROUND: OCT4, SOX2, and NANOG are major transcription factors related to stem cell self-renewal and differentiation. The aim of this study was to examine the association of OCT4, SOX2, and NANOG expression levels with the development and prognosis of patients with oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Expression levels of OCT4, SOX2, and NANOG were evaluated by immunohistochemistry with tissue microarray slides of 436 OSCC, 362 corresponding tumor-adjacent normal (CTAN) tissues, and 71 normal uvula epithelium tissues. The clinicopathologic and follow-up data of the OSCC patients were recorded. RESULTS: OCT4 expression was significantly higher in normal and CTAN tissues than in tumor tissue (both P < 0.001). SOX2 expression in CTAN tissue was significantly higher than that in normal (P = 0.021) and tumor tissues (P < 0.001). However, NANOG expression was significantly higher in CTAN (P = 0.014) and tumor tissues (P = 0.009) than in normal tissue. Higher OCT4 and SOX2 expressions were associated with earlier AJCC stage (P = 0.002 and P < 0.001), small tumor size (P = 0.017 and P = 0.001), and the absence of lymph node metastasis (P = 0.015 and P = 0.025). Higher levels of SOX2 expression were associated with better disease-specific survival (P = 0.002) even after adjustment for clinicopathologic factors. DISCUSSION: OCT4 and SOX2 are biomarkers of tumorigenesis and early stage OSCC. SOX2 is an independent prognostic factor for OSCC.
Asunto(s)
Biomarcadores de Tumor , Carcinoma de Células Escamosas/metabolismo , Progresión de la Enfermedad , Neoplasias de la Boca/metabolismo , Proteína Homeótica Nanog/biosíntesis , Factor 3 de Transcripción de Unión a Octámeros/biosíntesis , Factores de Transcripción SOXB1/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/biosíntesis , Biomarcadores de Tumor/genética , Carcinogénesis/genética , Carcinogénesis/patología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Femenino , Humanos , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/genética , Neoplasias de la Boca/patología , Proteína Homeótica Nanog/genética , Proteína Homeótica Nanog/metabolismo , Células Madre Neoplásicas/patología , Factor 3 de Transcripción de Unión a Octámeros/genética , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Pronóstico , Factores de Transcripción SOXB1/genética , Factores de Transcripción SOXB1/metabolismo , Factores de Transcripción/metabolismo , Adulto JovenRESUMEN
The clinical significance and biological function of DEXD/H box helicase 60 (DDX60) in oral cancer remains unknown. Herein, we evaluated the association of DDX60 expression with tumorigenesis and the prognosis of oral squamous cell carcinoma (OSCC). DDX60 expression was examined by immunohistochemistry on tissue microarray slides of 494 OSCC patients, including 180 buccal mucosal SCC (BMSCC), 241 tongue SCC (TSCC), and 73 lip SCC (LSCC) patients. DDX60 expression was significantly increased in all three subsites of OSCC compared to its expression in tumor adjacent normal tissues. However, its association with tumorigenesis was specific to the oral cavity subsite after the stratification of betel quid chewing, smoking, and drinking. Among OSCC patients, higher levels of DDX60 expression were associated with the male gender, a well-differentiated tumor, advanced stage of disease, and a large tumor size with subsite specific features. LSCC patients with high DDX60 expression levels showed shorter disease-specific survival, particularly those with moderately or poorly differentiated tumors. Additionally, TSCC or OSCC patients with high DDX60 expression showed a poor disease-free survival (DFS), particularly those with moderately or poorly differentiated tumors. Therefore, DDX60 is a novel and unfavorable biomarker for tumorigenesis and prognosis of OSCC in a subsite-specific manner.