Clinical significance of OCT4 and SOX2 protein expression in cervical cancer.
Clinical significance of OCT4 and SOX2 protein expression in cervical cancer.
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DOI：
10.1186/s12885-015-2015-1
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发表时间：
2015-12-26
期刊：
影响因子：
3.8
通讯作者：
Hewitt SM
中科院分区：
文献类型：
--
作者：
Kim BW;Cho H;Choi CH;Ylaya K;Chung JY;Kim JH;Hewitt SM
肿瘤干细胞标志物由于与肿瘤治疗中的放疗或化疗耐药性有关而成为研究热点。包括OCT 4和SOX 2在内的癌症干细胞标志物已在各种实体瘤中发现。本研究旨在探讨OCT 4和SOX 2在宫颈癌中的表达及其临床意义。为了确定OCT 4和SOX 2表达的临床意义，我们对305例正常宫颈上皮样本、289例宫颈上皮内瘤样病变样本和161例宫颈癌病例进行了OCT 4和SOX 2的免疫组化，并将数据与临床病理因素（包括宫颈癌患者的生存率）进行了比较。OCT 4和SOX 2在宫颈癌组织中的表达均高于正常宫颈组织（P均< 0.001）。OCT 4过表达与淋巴血管间隙浸润相关（p = 0.045），而SOX 2表达缺失与肿瘤大小相关（p = 0.015）。值得注意的是，OCT 4和SOX 2在癌前病变中显著共表达，但在恶性宫颈肿瘤中不表达。与低表达组相比，OCT 4过表达组的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SOX 2表达组的总生存率较好（p = 0.025）。考克斯回归分析显示，OCT 4是总生存期的独立风险因素（风险比= 11.23，95% CI，1.31 - 95.6; p = 0.027），而SOX 2过表达显示死亡的低风险比（风险比= 0.220，95% CI，0.06-0.72; p = 0.013）。这些结果表明，OCT 4过表达和SOX 2表达缺失与宫颈癌患者的不良预后密切相关。
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.