| BackgroundESCC is one of the most frequently diagnosed cancers in developing countries, especially in China. Recent epidemiological studies have shown that the incidence is increasing. Esophageal squamous cell carcinoma (ESCC) continues to be a significant cause of morbidity and mortality worldwide, and it is the fourth most common cause of cancer death in China.Currently, although therapy strategies have been improved, the prognosis of patients with ESCC is still poor and5-year survival rate for ESCC appears a dramatic decrease.ESCC shows a poor prognosis due to the lack of early screening strategy and is often presented in an advanced stage at the time of diagnosis, the widespread use of induction chemotherapy or chemotherapy and radiation therapy has not succeeded in improving overall survival.Therefore, the poor prognosis for most patients with ESCC has prompted the author to seek for novel molecular prognostic markers that helps identify patients at a higher risk of death and improve the prognosis of patients with ESCC. It is well exhibited that gene mutation is a key event in the occurrence and development of a variety of tumors. Based on the theory, the lower of cellular differentiation degree is more prone to develop malignant tumors. Thus, we could infer that cancer stem cells are most likely to form tumors, and more and more evidence show that tumor stem cells exist in tumor tissues.Cancer stem cells (CSCs) are a small sub-population of cancer cells that have stem cell-like properties such as self-renewal and the ability to differentiate into multiple cell types. However, most of these cancer stem cells are in a resting stage in the cell cycle, so tumor stem cells could keep clear of killing effect of chemotherapeutic, because that drugs used in chemotherapy only attack cells that are rapidly dividing. If the tumor stem cells have not been cleared, then relapse and metastasis may be inevitable. So, These data document that tumor stem cells play critical roles in the occurrence and development of tumors.Stem cell transcription factor SOX2belongs to group B of the SOX family with a high-mobility group DNA-binding domain,and plays critical roles in cell fate determination, differentiation and proliferation. SOX2is critical for the maintenance of pluripotency and self-renewal of embryonic stem cells and generation of induced pluripotent stem cells. In both humans and mice, SOX2is widely expressed during embryonic development throughout the entire epithelium of the brain and posterior neural tube,including the cortex, hippocampus, cerebellum, and spinal cord. In addition, persistent SOX2expression is observed in the developing eye, in particular in the lens, neural retina, and optic nerve. Endoderm-derived organs such as the trachea, esophagus,stomach,and posterior gut also express SOX2during embryogenesis. In the esophagus,SOX2plays an important role in differentiation and morphogenesis.Cancer cells,particularly in poorly differentiated and undifferentiated tumors,have been characterizde by numerous phenotypic traits that are similar to undifferentiated embryonic cells.These similarities suggest the expression of genes that participate in the regulation of stem cell properties.Researchs suggested that stem cell transcription factor SOX2has expressed in many tumor tissues.breast cancer,Liver cancer, soft tissue sarcoma, pancreatic carcinoma and so on had been confirmed. SOX2was reported to promote metastasis in various tumor tissues; SOX2improves metastasis of breast and prostate cancer cells by promoting epithelial-to-mesenchymal transition (EMT) through WNT/β-catenin.So SOX2plays an important role in the development of tumor.SOX2is a potential target for molecular therapy in the clinical treatment of patients with ESCC.However, the role for SOX2in ESCC has not yet been reported.To explore the expression patterns of stem cell transcription factor S0X2and its significance in diagnosis and prognosis in human esophageal squamous cell carcinoma,We made the following experiment.we hope the experiment could provide theoretical basis for the early diagnosis and prognosis of esophageal ESCC.ObjectiveTo explore the expression pattern of stem cell transcription factor SOX2and its significance in diagnosis and prognosis of human esophageal squamous cell carcinoma.MethodsThe expression of SOX2in esophageal squamous cancer cell lines KYSE450, KYSE140and KYSE70were characterized with the methods of real-time PCR, western blotting and immunocytochemistry. The expression of SOX2in79esophageal squamous cell carcinoma specimens was characterized with the method of immunohistochemistry. The correlation between the clinicopathological features and the expression of SOX2in the esophageal squamous cancer was analyzed with Crosstabs analysis, while survival curve regarding to the expression of SOX2was analyzed using the Kaplan-Meier method.Results1SOX2was variably expressed in three esophageal squamous cell carcinoma cell lines. Immunohistochemically, SOX2positive immunostaining was observed in the cancer cell nuclei.2Among79esophageal squamous cell carcinoma specimens,48(60.76%)were either negative or weakly positive for SOX2;19(20.05%)were moderately positive while12(15.19%)were strongly positive.3Crosstabs analysis showed that higher SOX2expression was significantly associated with higher histological grade and poorer overall survival. The relative risk of SOX2on prognosis of esophageal squamous cell carcinoma was1.962.ConclusionHigher expression level of stem cell transcription factor SOX2in esophageal squamous carcinomas was significantly associated with higher histological grade and poorer overall survival of patients, which made SOX2as the independent prognostic factor of survival. |
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