Kim Bo Wook, Cho Hanbyoul, Choi Chel Hun, Ylaya Kris, Chung Joon-Yong, Kim Jae-Hoon, Hewitt Stephen M
Experimental Pathology Lab, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, MSC 1500, Bethesda, MD, 20892, USA.
Department of Obstetrics and Gynecology, Kangdong Sacred Heart Hospital, Hallym University, Seoul, 135-701, South Korea.
BMC Cancer. 2015 Dec 26;15:1015. doi: 10.1186/s12885-015-2015-1.
Cancer stem cell markers have become a major research focus because of their relationship with radiation or chemotherapy resistance in cancer therapy. Cancer stem cell markers including OCT4 and SOX2 have been found in various solid tumors. Here, we investigate the expression and clinical significance of OCT4 and SOX2 in cervical cancer.
To define the clinical significance of OCT4 and SOX2 expression, we performed immunohistochemistry for OCT4 and SOX2 on 305 normal cervical epithelium samples, 289 cervical intraepithelial neoplasia samples, and 161 cervical cancer cases and compared the data with clinicopathologic factors, including survival rates of patients with cervical cancer.
OCT4 and SOX2 expression was higher in cervical cancer than normal cervix (both p < 0.001). OCT4 overexpression was associated with lymphovascular space invasion (p = 0.045), whereas loss of SOX2 expression was correlated with large tumor size (p = 0.015). Notably, OCT4 and SOX2 were significantly co-expressed in premalignant cervical lesions, but not in malignant cervical tumor. OCT4 overexpression showed worse 5-year disease-free and overall survival rates (p = 0.012 and p = 0.021, respectively) when compared to the low-expression group, while SOX2 expression showed favorable overall survival (p = 0.025). Cox regression analysis showed that OCT4 was an independent risk factor (hazard ratio = 11.23, 95 % CI, 1.31 - 95.6; p = 0.027) for overall survival while SOX2 overexpression showed low hazard ratio for death (hazard ratio = 0.220, 95 % CI, 0.06-0.72; p = 0.013).
These results suggest that OCT4 overexpression and loss of SOX2 expression are strongly associated with poor prognosis in patients with cervical cancer.
癌症干细胞标志物因其与癌症治疗中的放疗或化疗耐药性相关,已成为主要研究焦点。在各种实体瘤中已发现包括OCT4和SOX2在内的癌症干细胞标志物。在此,我们研究OCT4和SOX2在宫颈癌中的表达及临床意义。
为确定OCT4和SOX2表达的临床意义,我们对305例正常宫颈上皮样本、289例宫颈上皮内瘤变样本和161例宫颈癌病例进行了OCT4和SOX2的免疫组化检测,并将数据与临床病理因素进行比较,包括宫颈癌患者的生存率。
OCT4和SOX2在宫颈癌中的表达高于正常宫颈(两者p均<0.001)。OCT4过表达与脉管间隙浸润相关(p = 0.045),而SOX2表达缺失与肿瘤体积较大相关(p = 0.015)。值得注意的是,OCT4和SOX2在宫颈前病变中显著共表达,但在宫颈恶性肿瘤中并非如此。与低表达组相比,OCT4过表达的5年无病生存率和总生存率较差(分别为p = 0.012和p = 0.021),而SOX2表达显示总生存率良好(p = 0.025)。Cox回归分析显示,OCT4是总生存的独立危险因素(风险比=11.23,95%CI,1.31 - 95.6;p = 0.027),而SOX2过表达显示死亡风险比低(风险比=0.220,95%CI,0.06 - 0.72;p = 0.013)。
这些结果表明,OCT4过表达和SOX2表达缺失与宫颈癌患者的不良预后密切相关。