Abstract
Sox2 is thought to be an important regulator of self-renewal in embryonic stem cell. According to the cancer stem cell (CSC) theory, the overexpression of Sox2 is potentially involved in carcinogenesis and could affect tumor recurrence and metastasis. Previous study proved Sox2 might be prognostic marker for multiple human malignancies. The purpose of this study was to investigate the clinicopathological significance of Sox2 expression in human non-muscle-invasive bladder cancer. We examined Sox2 expression in 32 paired non-muscle-invasive bladder cancer tissues and adjacent non-cancerous tissues by quantitative real-time RT-PCR (qrtRT-PCR). In addition, we analyzed Sox2 and Ki-67 expression in 126 non-muscle-invasive bladder cancer samples and bladder cancer cell line T24 by immunohistochemistry and immunofluorescence assays. The recurrence-free survival was determined by Kaplan–Meier method and log-rank test. Cox regression was adopted for univariate and multivariate analyses of prognostic factors. The expression of Sox2 was significantly increased in non-muscle-invasive bladder cancer tissues. Sox2 expression was significantly correlated with that of Ki-67 (P < 0.001). The expression of Sox2 was significantly associated with tumor size (P = 0.006), tumor number (P = 0.037), and tumor grade (P < 0.001). Patients with high Sox2 expression had significantly poorer recurrence-free survival (P = 0.0002) when compared with patients with the low expression of Sox2. On multivariate analysis, Sox2 expression and tumor grade were found to be independent prognostic factors for recurrence-free survival (P < 0.05). Our data suggested for the first time that the high expression of Sox2 may contribute to the development of non-muscle-invasive bladder cancer and serve as a novel prognostic marker in patients with T1 bladder cancer.
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Acknowledgments
This work was supported by grants from the Science and Technology Development Foundation of Wuxi, China (CSE01N1108), Youth Foundation of Jiangsu Health Department, China (Q201207), Key Program of Hospital Management Center, China (YGZ1105). Foundation of Nanjing Medical University, China (njmu034). We thank Dr. Yuhong Xia (Department of Pathology, Affiliated Wuxi people’s hospital, Nanjing Medical University) for immunohistochemical analysis.
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Jun Ruan, Bingbing Wei, Zhuoqun Xu and Shudong Yang contributed equally to this work.
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Supplementary Fig. 1
Immunofluorescence staining of Sox2 in rat astrocytes. Sox2 showed positive nuclear staining in rat astrocytes (TIFF 3055 kb)
Supplementary Fig. 2
Immunohistochemical staining of Ki-67 in human bladder cancer. (a) Ki-67 showed negative staining in bladder cancer tissues, (b) showed low expression, and (c) showed high expression (TIFF 2566 kb)
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Ruan, J., Wei, B., Xu, Z. et al. Predictive value of Sox2 expression in transurethral resection specimens in patients with T1 bladder cancer. Med Oncol 30, 445 (2013). https://doi.org/10.1007/s12032-012-0445-z
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DOI: https://doi.org/10.1007/s12032-012-0445-z