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选定的上皮-间充质转化转录因子在子宫内膜癌中的表达。

Expression of Selected Epithelial-Mesenchymal Transition Transcription Factors in Endometrial Cancer.

机构信息

Department of Obstetrics and Gynecology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Torun, Bydgoszcz, Poland.

Department of Clinical Pathomorphology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Torun, Bydgoszcz, Poland.

出版信息

Biomed Res Int. 2020 Dec 29;2020:4584250. doi: 10.1155/2020/4584250. eCollection 2020.

Abstract

Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries. The aim of this study was to analyze the expression of SNAIL, SLUG, TWIST1, TWIST2, ZEB1, and ZEB 2 in primary tumor and the correlation with morphological and clinical characteristics of EC. The study included 158 patients with EC after surgical treatments: total hysterectomy and lymphadenectomy. The percentages of EC specimens testing positively for the EMT transcription factors were 84.5% for SNAIL, 92.2% for SLUG, 10.9% for TWIST1, 100% for TWIST2, 89% for ZEB1, and 98% for ZEB2. The expression of SLUG in patients with FIGO stage III or IV, type II EC, myometrial invasion ≥ 50% of the uterine wall thickness, and adnexal involvement and in patients with distant metastases was significantly higher. SLUG and ZEB2 expressions were identified as significant predictors of higher FIGO stages (III or IV) on univariate analysis. The overexpression of SLUG was a significant predictor of more aggressive type II EC, myometrial invasion ≥ 50% of the uterine wall thickness, and distant metastases on both univariate and multivariate analysis. Moreover, the overexpression of SLUG and ZEB2 was shown to be significant predictors of adnexal involvement on univariate analysis. ZEB 2 overexpression was identified in multivariate analysis as another independent predictor associated with a lesser likelihood of type II EC. Both univariate and multivariate analyses demonstrated that SLUG expression was the only predictor of 5-year survival in the study group. The overexpression of SLUG was associated with a significant increase in mortality hazard on univariate analysis and was shown to be a highly significant predictor of death on multivariate analysis. . Selected proteins of the EMT pathway play a role in endometrial carcinogenesis; SLUG and ZEB2 expressions in the primary tumor might predict clinical outcomes in EC and drive therapeutic decisions regarding adjuvant treatment in patients with this malignancy.

摘要

子宫内膜癌(EC)是发达国家最常见的妇科恶性肿瘤。本研究旨在分析 EMT 转录因子 SNAIL、SLUG、TWIST1、TWIST2、ZEB1 和 ZEB2 在原发性肿瘤中的表达,并与 EC 的形态学和临床特征进行相关性分析。本研究纳入了 158 例接受手术治疗(全子宫切除术和淋巴结切除术)的 EC 患者。EMT 转录因子在 EC 标本中呈阳性的比例分别为:SNAIL 为 84.5%、SLUG 为 92.2%、TWIST1 为 10.9%、TWIST2 为 100%、ZEB1 为 89%、ZEB2 为 98%。FIGO 分期为 III 或 IV 期、II 型 EC、肌层浸润≥50%子宫壁厚度和附件累及以及有远处转移的患者中 SLUG 的表达显著升高。SLUG 和 ZEB2 的表达在单因素分析中被确定为更高 FIGO 分期(III 或 IV)的显著预测因子。SLUG 的过表达是单因素和多因素分析中更具侵袭性 II 型 EC、肌层浸润≥50%子宫壁厚度和远处转移的显著预测因子。此外,SLUG 和 ZEB2 的过表达在单因素分析中被确定为附件累及的显著预测因子。ZEB2 的过表达在多因素分析中被确定为与 II 型 EC 可能性较小相关的另一个独立预测因子。单因素和多因素分析均表明,SLUG 表达是研究组 5 年生存的唯一预测因子。SLUG 的过表达与单因素分析中的死亡风险显著增加相关,并且在多因素分析中被证明是死亡的高度显著预测因子。 EMT 通路的选定蛋白在子宫内膜癌发生中起作用;原发性肿瘤中 SLUG 和 ZEB2 的表达可能预测 EC 的临床结局,并为该恶性肿瘤患者的辅助治疗决策提供依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/023e/7785369/f1e07bec0940/BMRI2020-4584250.001.jpg

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