Expression And Implication Of SOX2、SOX17and β-catenin In Cervical Squamous Cell Carcinoma

Backgroud and Objective:Cervical cancer is one of the most common gynecologic malignant tumors, whose incidence rate is the highest and is presenting a rising trend revealed by the increased incidence of young patient. It is threatening women’s health and life seriously. Up to now, the exact etiology of cervical cancer is not yet fully understood. But multi-factors and multi-stage pathological processes must have contributed to the development of cervical cancer undoubtedly, among which high-risk HPV infection is one of major factors. Nowadays, it is considered that the development of cervical cancer may be related to the disorders of signal pathways.SOX2is one of stem cell transcription factors, which plays an important role in the development of embryonic stem cell pluripotency, organ formation and neuronal differentiation in the early embryo. Studies showed that the occurrence and development of many tumors in human body had related to abnormal expression of SOX2.SOX17is one of tumor suppressor genes found in recent years, participating in the occurrence and development of tumors through its function of regulating Wnt signaling pathway.β--Catenin is one of multifunctional intracellular glucoproteins, which is the hub of the Wnt pathway and regulates cell biological functions through activating target genes in the signaling pathway.Recent studies showed that the occurrence and development of many tumors had related to disregulation of Wnt/β-catenin signaling pathway.SOX2and SOX17could interact with transfer factors to form protein complexes and regulate cell biological functions through balancing expression of target genes of Wnt signaling pathway.The expression of SOX2in cervical cancer havea rarly been reported in studies at home and abroad. While the expression of SOX17in cervical cancer have not been reported at home and abroad.This study aims to examine the role of SOX2、SOX17and β-catenin in the development of cervical squamous cell carcinoma and thus to provide certain theoretical basis for the diagnosis and novel therapy of cervical cancer by observing their expression levels respectively in normal cervical tissue, cervical intraepithelial neoplasia and cervical cancer, as well as relationship with different clinicopathological stages of cervical cancer.Materials and Methods1.GroupingAll tissue samples were collected from the department of pathology of the Second Affiliated Hospital of Zhengzhou University from March2010to September2011.60cases of cervical squamous cell carcinoma without radiotherapy and chemotherapy before surgery, confirmed by pathology diagnosis, were collected as experimental group.70(CINⅠ30, CINⅡ-Ⅲ40) cases of cervical intraepithelial neoplasia and20cases of normal cervical tissue from total hysterectomy because of fibromyoma were collected as control groups.2.MethodsThe expression levels of SOX2,SOX17and β-catenin in three groups were respectively detected by method of immunohistochemistry.3.Statistics AnalysisThe data was analyzed using SPSS17.0software and represented in the form of x±s. Differences among groups were analyzed using χ2test and the correlation analysis was operated using Spearson correlation analysis. P<0.05was thought to be statistically significant. Results1The expression of SOX2Positive expressions of SOX2are mainly located in cell membrane and (or) cytoplasm.Immunohistochemical analysis showed that the SOX2expression level increased gradually with the progression of cervical lesions. Positive expressions in cervical squamous cell carcinoma was significantly increased, compared with that in cervical intraepithelial neoplasia and normal cervical tissue (χ2=7.016P<0.05). Compared with the group of normal cervical tissue, the level in cervical squamous cell carcinoma CIN was significant increased (P<0.05). There was no significant difference between cervical CIN Ⅰ and CINII-Ⅲ (p>0.05). Moreover, pearson correlation analysis indicated that the expression level of SOX2was notably correlated with the clinical staging, histological grading of cervical cancer (P<0.05), while it was not notably correlated with the lymph node metastasis.(P>0.05).2The expression of SOX17Positive expressions of SOX17are mainly located in the nuclei with a few located in the cytoplasm or cell membranes. Immunohistochemical analysis showed that the SOX17expression level decreased gradually with the progression of cervical lesions. Positive expressions in the group of cervical intraepithelial neoplasia and cervical squamous cell carcinoma was significantly decreased, compared with in the group of normal cervical tissue (χ2=13.92P<0.05).Compared with cervical squamous cell carcinoma CIN, the level in the group of cervical squamous cell carcinoma was significant decreased (P<0.05). There was no significant difference between cervical CIN Ⅰ andCIN Ⅱ-Ⅲ (p>0.05). Besides,spearson correlation analysis indicated that the expression level of SOX17was notably correlated with the clinical staging of cervical cancer and the lymph node metastasis extent.(P<0.05).3The expression of β-cateninPositive expressions of β-catenin are mainly located in the cell membrane and (or) the cytoplasm. Immunohistochemical analysis showed that the β-catenin expression level increased gradually with the progression of cervical lesions. Positive expressions in the group of normal cervical tissue was significantly increased, compared with the group of cervical intraepithelial neoplasia and the group of cervical squamous cell carcinoma (χ2=17.490P<0.05). Compared with the group of cervical squamous cell carcinoma CIN, the level in the group of cervical squamous cell carcinoma was significant decreased (P<0.05). There was no significant difference between cervical CINI and CIN Ⅱ-Ⅲ (p>0.05).Furthermore, spearson correlation analysis manifested that the expression level of (3-catenin was notably correlated with the clinical staging, histological grading of cervical cancer (P<0.05), while it was not notably correlated with the lymph node metastasis extent.(P>0.05).4The correlation analysis of SOX2, SOX17and β-catenin expression in cervical squamous cell carcinomaSpearson correlation analysis showed that the SOX17expression was negatively correlated with β-catenin expression (χ2=8.013P<0.05; r=-0.369). SOX2expression was positively correlated withβ-catenin expression (χ2=12.739P<0.05; r=0.465), while there was no correlation between SOX2and SOX17(P>0.05).Conclusions1SOX2was highly expressed in cervical squamous cell carcinoma tissues and closely related to the clinicopathological grades of cervical cancer, which indicated SOX2might play a role in the development of cervical squamous cell carcinoma.2SOX17had high expression in normal cervical tissue but low expression in cervical squamous cancer, suggesting that its low expression might relevantand the pathogenesis of cervical squamous cell carcinoma.3SOX17, SOX2and β-catenin might be synergisticly involved in the occurrence and the development of cervical squamous cell carcinoma.