人子宫内膜癌中Notch和Wnt信号分子表达的变化
Changes in the expression of Notch and Wnt signalling molecules in human endometrial cancer.
作者信息
Lachej Nadežda, Jonušienė Violeta, Mažeikė Augustina, Sasnauskienė Aušra, Dabkevičienė Daiva, Šimienė Julija, Sužiedėlis Kęstutis, Didžiapetrienė Janina
机构信息
Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Clinic of Internal Diseases, Family Medicine and Oncology, Vilnius, Lithuania.
National Cancer Institute, Vilnius, Lithuania.
出版信息
Acta Med Litu. 2019;26(3):181-190. doi: 10.6001/actamedica.v26i3.4148.
BACKGROUND
Endometrial cancer is the sixth most frequent type of cancer among women worldwide. Type I adenocarcinomas account for 80-85% of endometrial cancer cases and sometimes require more aggressive treatment than the remaining part of this group. Therefore, molecular markers to stratify adenocarcinomas are needed.
MATERIALS AND METHODS
In this study, we analysed Notch and Wnt signalling in human endometrial cancer cases to evaluate these pathway elements as potential biomarkers for type I endometrial cancer. Endometrial samples were obtained from 47 women undergoing surgery for stage I-IV endometrial cancer in the National Cancer Institute (Vilnius, Lithuania) in 2015-2016. The expression at the mRNA level of signalling molecules genes (, , , , , , , , and ) was analysed by the quantitative real-time polymerase chain reaction. Relative expression of NOTCH1, NOTCH4, HES1 and β-catenin proteins in endometrioid adenocarcinoma was evaluated by the Western blot method.
RESULTS
The expression level of Notch receptors, ligands, and the target gene as well as and , was reduced in stage I endometrioid adenocarcinoma if compared to the adjacent non-tumour tissue. The expression of all receptors, ligands, and target molecules was reduced in adenocarcinomas of later stages. The statistically significant correlations between transcript amounts of Notch receptors and ligands were found. There was a statistically significant difference in the gene expression of Notch signalling pathway components between different tumour differentiation grade samples. A positive correlation between mRNA and protein the expression level of NOTCH1, NOTCH4, HES1 was determined in stage I samples.
CONCLUSIONS
Analysis of 47 human endometrial cancer samples revealeda reduction in the transcript levels of Notch and Wnt signalling molecule compared to the adjacent non-tumour tissue. These results suggest tumour suppressor function of Notch and Wnt signalling in human endometrial cancer. More detailed research on these signalling pathways should reveal their importance as potential biomarkers.
背景
子宫内膜癌是全球女性中第六大常见癌症类型。I型腺癌占子宫内膜癌病例的80 - 85%，有时需要比该组其他类型更积极的治疗。因此，需要用于对腺癌进行分层的分子标志物。
材料与方法
在本研究中，我们分析了人类子宫内膜癌病例中的Notch和Wnt信号通路，以评估这些通路元件作为I型子宫内膜癌潜在生物标志物的可能性。2015 - 2016年从立陶宛维尔纽斯国家癌症研究所47例接受I - IV期子宫内膜癌手术的女性中获取子宫内膜样本。通过定量实时聚合酶链反应分析信号分子基因（ 、 、 、 、 、 、 、 和 ）的mRNA水平表达。采用蛋白质印迹法评估子宫内膜样腺癌中NOTCH1、NOTCH4、HES1和β - 连环蛋白的相对表达。
结果
与相邻非肿瘤组织相比，I期子宫内膜样腺癌中Notch受体、配体以及靶基因以及 和 的表达水平降低。后期腺癌中所有受体、配体和靶分子的表达均降低。发现Notch受体和配体的转录量之间存在统计学显著相关性。不同肿瘤分化程度样本之间Notch信号通路成分的基因表达存在统计学显著差异。在I期样本中确定了NOTCH1、NOTCH4、HES1的mRNA与蛋白质表达水平之间呈正相关。
结论
对47例人类子宫内膜癌样本的分析显示，与相邻非肿瘤组织相比，Notch和Wnt信号分子的转录水平降低。这些结果表明Notch和Wnt信号在人类子宫内膜癌中具有肿瘤抑制功能。对这些信号通路进行更详细的研究应能揭示它们作为潜在生物标志物的重要性。
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