Expression Of Oct4, Sox2 And Nanog And Its Clinical Significance In Tongue Squamous Cell Carcinoma

Background and objectives: Cancer stem cells have been proposed to be responsible for tumorigenicity and development;promote cancer relapse and metastasis.These important transcription factors Oct4, Sox2 and Nanog, play an important role in the maintenance of embryonic stem cell pluripotency and self-renewal. Recently, the stemness factors Oct4, Sox2 and Nanog were associated with induced pluripotent stem cells, suggesting a correlation between these stemness factors and cancer stem cells. This study investigated Oct4, Sox2 and Nanog protein expression in tongue squamous cell carcinoma(TSCC) and statistically analyzed the relationships between the expressions of Oct4, Sox2 and Nanog with both clinicopathological characteristics and survival of patients with TSCC. We explored the role and clinical significance of stemness factors in tumorigenicity and development of TSCC.Materials and Methods: The paraffin tissue specimens collected were surgical resection specimens of 51 patients with histologically conformed TSCC and with complete clinical follow-up data who presented to the Oral and Maxillofacial Surgery of the Stomatological Hospital Affiliated to Nan Chang University between January 2005 to December 2009. Immunohistochemistry was employed to detect the protein expression levels of Oct4, Sox2 and Nanog in 51 TSCC tissue samples. The results were statistically analysed by using IBM SPSS20.0 software to study their relationships with both clinicopathological features and survival of patients with TSCC and their mutal relations.Results: Oct4, Sox2 and Nanog positive expression rates were: 84.3%(43/51), 92.2%(47/51), 80.4%(41/51) in TSCC,respectively. Kruskal—Wallis H test showed that Oct4, Sox2 and Nanog expression levels were significantly correlated with the histological grade of TSCC(p = 0.004 <0.01, p = 0.006 <0.01, p = 0.002 <0.01, respectively). Oct4, Sox2, Nanog expression levels were not significantly correlated with age, gender, T stage, Tobacco smoking and Alcohol consumption status, but Oct4 expression level was significantly associated with lymph node metastasis(p = 0.001 <0.01), Sox2 and Nanog expression levels were not significantly associated with lymph node metastasis(p> 0.05). Speaman correlation analysis revealed that the expression of Sox2 and Nanog were significantly correlated with Oct4(p<0.001, p=0.002 <0.01,respectively), that Sox2 and Nanog were not related(p = 0.402> 0.05). Kaplan-Meier analysis revealed Oct4, Sox2, Nanog expression were associated with poor overall survival of patients with TSCC(p = 0.001 <0.01, p = 0.002 <0.01, p = 0.006 <0.01, respectively),triple-strong cases had the poorest overall survival(p = 0.001 <0.01). Multivariate Cox proportional hazards regression model showed that Sox2, Nanog, lymph node metastasis were independent prognostic factors of overall survival in patients with TSCC(p = 0.027 <0.05, p = 0.040 <0.05, p = 0.002 <0.01, respectively).Conclusion: Oct4, Sox2 and Nanog expression levels were significantly correlated with the histological grade of TSCC,suggesting that Oct4, Sox2 and Nanog may be related to differentiation of TSCC cells. The expression of Sox2 and Nanog were positively correlated with Oct4,suggesting that Oct4, Sox2 and Nanog may explore coordinated function in tongue squamous cell carcinoma;that combined detection of Oct4, Sox2, Nanog may more accurately reflect the biological behavior of tongue squamous cell carcinoma.Sox2, Nanog, lymph node metastasis had independent prognostic effects on overall survival,suggesting that SOX2, Nanog expression may be an usefull indicator for predicting the prognosis of patients with TSCC.