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TTF-1 和 PTEN 在早期子宫内膜癌中的表达及意义。

Expressions and significances of TTF-1 and PTEN in early endometrial cancer.

机构信息

Department of Pathology, Jining No. 1 People's Hospital, Jining, Shandong Province, China.

出版信息

Eur Rev Med Pharmacol Sci. 2017 Jul;21(3 Suppl):20-26.

Abstract

OBJECTIVE

To analyze the expressions and significances of TTF-1 (Thyroid transcription factor-1) and PTEN (Phosphatase and tensin homolog) in early endometrial cancer.

PATIENTS AND METHODS

41 patients with endometrial cancer, 38 patients with proliferative endometrium and 13 patients with normal endometrium, were selected. The fluorescence quantitative PCR (polymerase chain reaction) was used to detect the expression levels of TFF-1 and PTEN mRNAs (Messenger ribonucleic acids) in the above three endometria, and their relations with clinical pathological characteristics were analyzed. The RT-PCR (reverse transcription-polymerase chain reaction) was employed to detect the expression levels of miR-135b, miR-125b and Snail mRNAs in the three endometria, and their correlations with the expressions of TTF-1 and PTEN mRNAs, were analyzed.

RESULTS

The expression levels of TFF-1 and PTEN mRNAs in endometrial cancer tissues were significantly lower than those in the other two groups, while those in normal endometrium tissues were the highest, and the differences were statistically significant (p < 0.05). There were no significant differences in the menstruation status and the expression levels of TFF-1 and PTEN mRNAs between adenocarcinoma and squamous carcinoma (p > 0.05). With the increase of FIGO (International Federation of Gynecology and Obstetrics) stage and depth of invasion, as well as the metastasis of pelvic lymph nodes, the expression levels of TFF-1 and PTEN mRNAs were significantly decreased, and the differences were statistically significant (p < 0.05). The expression level of miR-135b mRNA in endometrial cancer was significantly higher than that in the other two groups, while that in normal endometrium was the lowest. The expression levels of miR-125b and Snail mRNAs were significantly lower than those in the other two groups, while those in normal endometrium were the highest; the differences were statistically significant (p < 0.05). Expression levels of TTF-1 and PTEN mRNAs were negatively correlated with the expression level of miR-135b mRNA, and positively associated with the expression levels of miR-125b and Snail mRNAs (p < 0.05). The results from the ROC (Receiver Operating Characteristic) model showed that, for the diagnosis of endometrial cancer with TTF-1 mRNA, the sensitivity was 86.5%, the specificity was 84.2%, the accuracy (area under curve - AUC) was 0.823, 95% CI (confidence intervals) = 0.762-0.921, p = 0.012. For the diagnosis of endometrial cancer with PTEN mRNA, the sensitivity was 85.3%, the specificity was 83.6%, the accuracy was 0.842, 95% CI = 0.785-0.936, p = 0.010.

CONCLUSIONS

TTF-1 and PTEN can be used as molecular markers for the early diagnosis of endometrial cancer, which are closely related to clinical features and may affect tumor progression by regulating the proliferation activity of tumor cells.

摘要

目的

分析甲状腺转录因子-1(TTF-1)和磷酸酶及张力蛋白同源物(PTEN)在早期子宫内膜癌中的表达及意义。

患者与方法

选取子宫内膜癌患者 41 例、增生期子宫内膜患者 38 例和正常子宫内膜患者 13 例,采用荧光定量 PCR 检测三组子宫内膜中 TFF-1 和 PTEN mRNA 的表达水平,并分析其与临床病理特征的关系。采用 RT-PCR 检测三组子宫内膜中 miR-135b、miR-125b 和 Slug mRNA 的表达水平,并分析其与 TTF-1 和 PTEN mRNA 表达的相关性。

结果

子宫内膜癌组织中 TFF-1 和 PTEN mRNA 的表达水平明显低于其他两组,而正常子宫内膜组织中的表达水平最高,差异均有统计学意义(P<0.05)。腺癌和鳞癌患者的 TFF-1 和 PTEN mRNA 的表达水平及月经状态差异均无统计学意义(P>0.05)。随着国际妇产科联盟(FIGO)分期和浸润深度的增加以及盆腔淋巴结转移,TFF-1 和 PTEN mRNA 的表达水平明显降低,差异均有统计学意义(P<0.05)。子宫内膜癌组织中 miR-135b mRNA 的表达水平明显高于其他两组,而正常子宫内膜组织中的表达水平最低。miR-125b 和 Slug mRNA 的表达水平明显低于其他两组,而正常子宫内膜组织中的表达水平最高,差异均有统计学意义(P<0.05)。TTF-1 和 PTEN mRNA 的表达水平与 miR-135b mRNA 的表达水平呈负相关,与 miR-125b 和 Slug mRNA 的表达水平呈正相关(P<0.05)。ROC 模型结果显示,以 TTF-1 mRNA 诊断子宫内膜癌的敏感度为 86.5%,特异度为 84.2%,准确度(曲线下面积-AUC)为 0.823,95%CI(置信区间)为 0.762-0.921,P=0.012。以 PTEN mRNA 诊断子宫内膜癌的敏感度为 85.3%,特异度为 83.6%,准确度为 0.842,95%CI 为 0.785-0.936,P=0.010。

结论

TTF-1 和 PTEN 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,可能通过调节肿瘤细胞的增殖活性而影响肿瘤的进展。

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