维吾尔族妇女宫颈癌发生与ALDH1A1基因表达调控的关系及临床意义

摘要

目的 本研究利用新疆维吾尔族妇女宫颈癌标本资源,对ALDH1A1基因的mRNA和蛋白质表达水平进行定量分析,探讨宫颈癌发生与该基因表达调控的关系及临床意义.方法 收集维吾尔族妇女宫颈鳞癌(cervical squamous cell carcinoma,CSCC)、宫颈内上皮内瘤变(cervical intraepithelial neoplasia,CIN)Ⅱ～Ⅲ及宫颈炎患者的新鲜组织标本58例和石蜡包埋组织切片75例,利用荧光定量RT-PCR方法、免疫组织化学等方法检测ALDH1A1基因在宫颈病变组织中的表达水平变化.结果 ALDH1A1 mRNA在宫颈癌组织中的表达量(1.733±0.968),显著高于正常宫颈组织中的表达量(0.458±0.347,P＜0.05).随着宫颈病变的进程ALDH1A1蛋白的表达升高,ALDH1A1蛋白在官颈癌组织中表达率为77.5％ (31/40),显著高于正常宫颈组织中的表达率36.8％ (7/19) (P ＜0.01).单一基因表达水平检测对宫颈癌诊断的特异性和敏感度分析,该基因的曲线下面积均＞0.7,说明上述基因检测的诊断准确度较高,对宫颈癌有一定的预警价值,推测ALDH1A1基因的高表达可能成为宫颈癌早期预警的标志物.结论 ALDH1A1可作为宫颈癌肿瘤干细胞特异标志物,该基因转录表达上调或蛋白质表达水平升高与维族妇女宫颈癌发生有密切关系,可能成为肿瘤诊断和预后的分子标志物.%Objective To investigate the association of regulation of ALDH1 A1 expressions with cervical carcinogenesis by quantitatively analyzing the mRNA and protein expression level of this gene in cervical carcinoma and its precursor lesions in Uighur women.Methods A total of 58 fresh tissue samples and 75 paraffin-embedded tissue slides were collected from Uighur women with CSCC,cervical intraepithelial neoplasia(CIN) Ⅱ-Ⅲ and cervicitis.The mRNA and protein expression of ALDH1 A1 gene was determined by quantitative RT-PCR and immunohistochemistry,respectively.Results The mRNA expression level of ALDH1A1 in CSCC (1.733 ± 0.968)was significantly higher than cervicitis(0.458 ± 0.347) (P ＜ 0.05).The immunohistochemistry results showed that the protein expression level of ALDH1A1 was remarkably increased with development of the cervical lesions.A Significantly higher expression of AL-DH 1 A 1 protein in CSCC77.5 ％ (31/40) than in cervicitis36.8 ％ (7/19) (P ＜ 0.01) was seen.The analysis of specificity and sensitivity in the detection ALDH1 A1 gene expression showed that the detection of ALDH1A1 had a high accuracy based on AUC which was bigger than 0.70,suggested that the detection of above gene had an impact in early prognosis of cervical cancer.we can infer ALDH1 A1 expres sion differences could become cervical cancer early warning markers.Conclusion ALDH1A1 can be used as cervical cancer stem cell markers.The up-regulation of ALDH1 A1 at the transcriptional and translational level was closely associated with the development of cervical cancer in Uighur women,and ALDH1A1 may become a molecular marker for the diagnosis and prognosis of CSCC.