TTF-1和PTEN基因在子宫内膜癌早期病变中的表达意义

摘要

目的 分析甲状腺转录因子-1(TTF-1)和磷酸酶与张力蛋白同源物(PTEN)基因在子宫内膜癌早期病变中的表达意义.方法 选择子宫内膜癌41例、 增生性子宫内膜38例和正常子宫内膜13例,采用荧光定量PCR法(RT-PCR)检测3种子宫内膜中TTF-1和PTEN mRNA表达量,分析其与临床病理特征的关系;RT-PCR法检测3种子宫内膜中miR-135b、miR-125b和Snail mRNA表达量,分析其与TTF-1和PTEN mRNA表达量的相关性.结果 子宫内膜癌组织中TTF-1和PTEN mRNA表达量显著低于其他2组,正常子宫内膜组织中表达量最高,差异有统计学意义(P<0.05).绝经与否、腺癌和鳞癌间TTF-1和PTEN mRNA表达水平比较,差异无统计学意义(P>0.05);FIGO分期增加、肌层浸润增加、盆腔淋巴结转移的TTF-1和PTEN mRNA表达水平明显降低,差异有统计学意义(P<0.05).子宫内膜癌中miR-135b mRNA的表达水平显著高于其他2组,正常子宫内膜中最低;miR-125b和Snail mRNA的表达水平显著低于其他2组,正常子宫内膜中最高;差异有统计学意义(P<0.05).TTF-1和PTEN mRNA表达量与miR-135b mRNA表达量呈负相关,与miR-125b和Snail mR-NA表达量呈正相关(P<0.05).ROC模型得出,TTF-1 mRNA诊断子宫内膜癌的敏感性86.5%,特异性84.2%,准确性0.823,95%CI=0.762~0.921,P=0.012;PTEN mRNA诊断子宫内膜癌的敏感性85.3%,特异性83.6%,准确性0.842,95%CI=0.785~0.936,P=0.010.结论 TTF-1和PTEN基因可作为子宫内膜癌早期诊断的分子标志物,与临床特征密切相关,可能通过调控肿瘤细胞增殖活性影响肿瘤进程.%Objective To study the significance of thyroid transcription factor-1(TTF-1)and phosphatase and tensin homolog(PTEN)genes expression in early endometrial cancer.Methods A total of 41 consecutives as endometrial cancer,38 patients with hyperplastic endometrium and 13 cases of normal endometrium were enrolled, then we detected the levels of TTF-1 and PTEN mRNA in the three endometrium tissues by fluorescent quantitative PCR(RT-PCR),and analyzed the relationship between them and clinicopathological features;the correlation of TTF-1 and PTEN mRNA to miR-135b,miR-125b and Snail mRNA levels in the three endometrium tissues by RT-PCR.Results The levels of TTF-1 and PTEN mRNA in endometrial cancer tissue were both significantly lower than the other two,and were the highest in normal endometrium(P<0.05).The expressions of TTF-1 and PTEN were no relationship to menopause,adenocarcinoma or squamous cell carcinoma(P>0.05);while they were lower as FIGO classes,myometrial invasion and pelvic lymph node metastasis were increasing(P<0.05).The level of miR-135b mRNA in endometrial cancer tissue was significantly higher,while miR-125b and Snail mRNA were lower than the other two,miR-135b mRNA level in normal endometrium was the lowest,miR-125b and Snail mRNA was the highest(P<0.05).The TTF-1 and PTEN mRNA expressions were positively ralted to miR-135b mRNA level,while negatively related to miR-125b and Snail mRNA.The diagnosed sensitivity of TTF-1 mRNA for endometrial cancer was 86.5%,specificity 84.2%,accuracy 0.823,95% CI=0.762~0.921,P=0.012 by ROC model;while they were 85.3%,83.6%,0.842,95% CI=0.785~0.936,P=0.010 of PTEN mRNA correspondingly.Conclusion TTF-1 and PTEN genes can be the molecular markers for early diagnosis of endometrial cancer,are related to clinical features,and may influence tumor by regulating tumor cell proliferation activity.