Roškar Luka, Kokol Marko, Pavlič Renata, Roškar Irena, Smrkolj Špela, Rižner Tea Lanišnik
Department of Gynaecology and Obstetrics, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia.
Division of Gynaecology and Obstetrics, General Hospital Murska Sobota, 9000 Murska Sobota, Slovenia.
Cancers (Basel). 2023 Jul 18;15(14):3661. doi: 10.3390/cancers15143661.
Endometrial cancer (EC) is an increasing health concern, with its growth driven by an angiogenic switch that occurs early in cancer development. Our study used publicly available datasets to examine the expression of angiogenesis-related genes and proteins in EC tissues, and compared them with adjacent control tissues. We identified nine genes with significant differential expression and selected six additional antiangiogenic genes from prior research for validation on EC tissue in a cohort of 36 EC patients. Using machine learning, we built a prognostic model for EC, combining our data with The Cancer Genome Atlas (TCGA). Our results revealed a significant up-regulation of IL8 and LEP and down-regulation of eleven other genes in EC tissues. These genes showed differential expression in the early stages and lower grades of EC, and in patients without deep myometrial or lymphovascular invasion. Gene co-expressions were stronger in EC tissues, particularly those with lymphovascular invasion. We also found more extensive angiogenesis-related gene involvement in postmenopausal women. In conclusion, our findings suggest that angiogenesis in EC is predominantly driven by decreased antiangiogenic factor expression, particularly in EC with less favourable prognostic features. Our machine learning model effectively stratified EC based on gene expression, distinguishing between low and high-grade cases.
子宫内膜癌(EC)是一个日益受到关注的健康问题,其生长由癌症发展早期发生的血管生成转换驱动。我们的研究使用公开可用的数据集来检查EC组织中血管生成相关基因和蛋白质的表达,并将它们与相邻的对照组织进行比较。我们鉴定出九个具有显著差异表达的基因,并从先前的研究中选择了另外六个抗血管生成基因,在36名EC患者的队列中对EC组织进行验证。使用机器学习,我们结合我们的数据与癌症基因组图谱(TCGA)构建了一个EC的预后模型。我们的结果显示,EC组织中IL8和LEP显著上调,其他十一个基因下调。这些基因在EC的早期阶段和低级别以及没有深肌层或淋巴管浸润的患者中表现出差异表达。基因共表达在EC组织中更强,特别是那些有淋巴管浸润的组织。我们还发现绝经后女性中血管生成相关基因的参与更为广泛。总之,我们的研究结果表明,EC中的血管生成主要由抗血管生成因子表达降低驱动,特别是在预后特征较差的EC中。我们的机器学习模型基于基因表达有效地对EC进行分层,区分低级别和高级别病例。