干细胞相关转录因子OCT4在宫颈癌组织和外周血中的表达及其临床意义

The expression and clinical significance of stem cell related transcription factor OCT4 in cervical cancer tissues and peripheral blood

目的:检测宫颈癌及病变组织内肿瘤干细胞关键因子八聚体结合转录因子4(OCT4)的mRNA及组织蛋白表达量,同时对外周血血浆OCT4含量进行定量检测,并探讨其在宫颈癌发生、发展、浸润及转移中的作用。方法:采用荧光定量RT-PCR、酶联免疫吸附法(ELISA)和免疫组织化学等分子生物学方法,对OCT4mRNA、组织蛋白及血浆蛋白含量进行定量检测,并运用统计学ROC曲线进一步评价该指标的准确度、特异度与灵敏度。结果:(1)OCT4 mRNA在宫颈癌组织中的表达量(1.733±0.968)显著高于宫颈上皮内瘤变(CINⅡ-Ⅲ)组织(1.697±1.431)和宫颈炎组织(0.636±0.374),组间比较差异有统计学意义,P<0.05;(2)通过免疫组织化学鉴定,随着宫颈病变恶性程度增高OCT4蛋白的表达率升高,OCT4蛋白在宫颈癌组织中表达率为80%(32/40),显著高于宫颈炎组织中的表达率31.57%(6/19),且P<0.05;(3)ELISA结果显示,宫颈癌与CINⅡ-Ⅲ或慢性宫颈炎比较,OCT4血浆含量差异有统计学意义(P<0.05),但CINⅡ-Ⅲ与炎症的差异无统计学意义(P>0.05)。(4)在绘制ROC曲线后发现,OCT4基因的曲线下面积(AUC)是0.895,OCT4血浆含量检测的AUC为0.773,OCT4基因和血浆含量检测的诊断准确度较高。结论:肿瘤干细胞标志物OCT4表达上调对宫颈癌的诊断可提供可靠的实验数据,该转录因子在组织和血浆中的表达情况很可能成为预后生物标志物或治疗靶标。

Objective:To detect the key factor of tumor stem cell octamer binding transcription factor 4(OCT4)mRNA and tissue protein expression in cervical cancer,and to quantitatively detect the plasma protein content of OCT4 in peripheral blood,and to explore its occurrence,development,infiltration and transfer in cervical cancer.Methods:Fluorescence quantitative RT-PCR,enzyme-linked immunosorbent assay(ELISA)and immunohistochemistry were used to quantitatively detect OCT4 mRNA,tissue protein and plasma protein content,and statistical ROC curve was used to further evaluate the accuracy,specificity and sensitivity of this indicator.Results:(1)The expression of OCT4 mRNA in cervical cancer tissues(1.733±0.968)clearly exceeded the expression in CINⅡ-Ⅲtissues(1.697±1.431)and cervicitis tissues(0.636±0.374),and there were significant differences,P<0.05;(2)immunohistochemistry result showed that with the increase of malignant degree of cervical lesions,the expression rate of OCT4 protein increased,and the expression rate of OCT4 protein in cervical cancer tissue was80%(32/40),which was significantly higher than the expression rate in cervicitis tissue 31.57%(6/19),and P<0.05;(3)ELISA test results in peripheral blood showed that comparing cervicat cancer with CINⅡ-Ⅲor chronic cervicitis,the difference in plasma concentration of OCT4 was statistically significant(P<0.05),but the difference between CINⅡ-Ⅲand inflammation group was not statistically significant(P>0.05).(4)After drawing the ROC curve,the area under the curve(AUC)of the OCT4 gene was 0.895.Next,the author started from the OCT4 concentration and focused on the analysis of specificity and sensitivity,AUC of OCT4 plasma level was 0.773.Obviously,the detection accuracy of OCT4 gene and plasma level was relatively high.Conclusion:The expression of tumor stem cell marker OCT4 is up-regulated,which provides reliable experimental data for the diagnosis of cervical cancer.The expression of this transcription factor in tissue and plasma is likely to become a prognostic biomarker or therapeutic target.