Department of Obstetrics & Gynecology, Chinese People's Liberation Army (PLA) Medical School, No. 28, Fuxing Road, Haidian District, Beijing 100853, China.
Department of Obstetrics and Gynecology, Seventh Medical Center of Chinese PLA General Hospital, No. 5, Nanmencang, Dongsishitiao, Dongcheng District, Beijing 100700, China.
Genes (Basel). 2022 May 24;13(6):935. doi: 10.3390/genes13060935.
Endometrial carcinoma (EC), a common female reproductive system malignant tumor, affects thousands of people with high morbidity and mortality worldwide. This study was aimed at developing a prediction model for the diagnosis of EC in the general population. First, we obtained datasets GSE63678, GSE106191, and GSE115810 from the Gene Expression Omnibus (GEO) database, dataset GSE17025 from the GEO database, and the RNA sequence of EC from The Cancer Genome Atlas (TCGA) database to constitute the training, test, and validation groups, respectively. Subsequently, the 96 most significantly differentially expressed genes (DEGs) were identified and analyzed for function and pathway enrichment in the training group. Next, we acquired the disease-specific genes by random forest and established an artificial neural network for the diagnosis. Receiver operating characteristic (ROC) curves were utilized to identify the signature across the three groups. Finally, immune infiltration was analyzed to reveal tumor-immune microenvironment (TIME) alterations in EC. The top 96 DEGs (77 down-regulated and 19 up-regulated genes) were primarily enriched in the interleukin-17 signaling pathway, protein digestion and absorption, and transcriptional misregulation in cancer. Subsequently, 14 characterizing genes of EC were identified by random forest. In the training, test, and validation groups, the artificial neural network was constructed with high diagnostic accuracies of 0.882, 0.864, and 0.839, respectively, and areas under the ROC curve (AUCs) of 0.928, 0.921, and 0.782, respectively. Finally, resting and activated mast cells were found to have increased in TIME. We constructed an artificial diagnostic model with excellent reliability for EC and uncovered variations in the immunological ecosystem of EC through integrated bioinformatics approaches, which might be potential diagnostic targets for EC.
子宫内膜癌(EC)是一种常见的女性生殖系统恶性肿瘤,在全球范围内影响着成千上万的人,发病率和死亡率都很高。本研究旨在建立一种用于一般人群中 EC 诊断的预测模型。首先,我们从基因表达综合数据库(GEO)中获取数据集 GSE63678、GSE106191 和 GSE115810,从 GEO 数据库中获取数据集 GSE17025,从癌症基因组图谱(TCGA)数据库中获取 EC 的 RNA 序列,分别构成训练组、测试组和验证组。随后,我们在训练组中识别和分析了 96 个最显著差异表达基因(DEGs)的功能和通路富集。接下来,我们通过随机森林获得疾病特异性基因,并建立人工神经网络进行诊断。我们利用受试者工作特征(ROC)曲线在三组中识别该特征。最后,我们分析免疫浸润以揭示 EC 中的肿瘤免疫微环境(TIME)变化。前 96 个 DEGs(77 个下调基因和 19 个上调基因)主要富集在白细胞介素-17 信号通路、蛋白质消化吸收和癌症转录失调中。随后,我们通过随机森林确定了 14 个 EC 特征基因。在训练组、测试组和验证组中,人工神经网络的构建具有 0.882、0.864 和 0.839 的高诊断准确率,ROC 曲线下面积(AUC)分别为 0.928、0.921 和 0.782。最后,我们发现静止和激活的肥大细胞在 TIME 中增加。我们通过综合生物信息学方法构建了一种具有出色可靠性的 EC 人工诊断模型,并揭示了 EC 免疫生态系统的变化,这些可能是 EC 的潜在诊断靶点。