Identification of prognostic biomarkers for endometrioid endometrial carcinoma based on the miRNA and mRNA co‐expression network regulated by estradiol

IF 2.2 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL
Qiu Xie , Junting Huang , Yuan Xie , Jin Hu , Li Jin
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引用次数: 0

Abstract

Background

Endometrioid Endometrial Carcinoma (EEC), an estradiol-related disease, remains a serious health threat to women because of its high incidence and trend of rejuvenation. Accumulating evidence has highlighted that microRNAs (miRNAs) and messenger RNAs (mRNAs) play important roles in various biological processes involved in the pathogenesis of EEC. This study aimed to identify the potential prognostic biomarkers associated with EEC regulated by estradiol.

Methods

RNA expression profiles of EEC were obtained from The Cancer Genome Atlas database (n = 408) and the original sequencing, which was performed on endometrial cancer Ishikawa cells treated with 250 nM estradiol (n = 3), 50 nM estradiol (n = 3) or control (n = 3). The TargetScan database was used to predict the target genes of prognosis-related differentially expressed miRNAs (DEMs). Subsequently, functional enrichment analysis and topological analysis were performed on the overlaps of target genes and differentially expressed mRNAs (DEGs). Kaplan-Meier analysis was used to predict prognosis‐related target genes to identify prognostic biomarkers and cell population landscapes, and gene expression analysis was performed to locate prognosis-related DEGs based on single-cell transcriptomic sequencing data from the NCBI Sequence Read Archive database.

Results

Four estradiol-related DEGs were associated with prognosis, and 235 overlapping target DEGs were screened and incorporated into the functional enrichment analysis and protein-protein interaction network visualization studies. Additionally, SACS and GPR157 were identified as potential biomarkers for EEC prognosis through survival analyses. Furthermore, single-cell transcriptome data were analyzed to show changes in gene expression levels in specific cell types.

Conclusions

This study demonstrates that miR-142–5p–SACS and miR-30a-5p–GPR157, which are regulated by estradiol, may hold promise as diagnostic and prognostic biomarkers and novel therapeutic targets for EEC.
基于雌二醇调控的miRNA和mRNA共表达网络的子宫内膜样子宫内膜癌预后生物标志物鉴定
子宫内膜癌(EEC)是一种与雌二醇相关的疾病,由于其高发病率和年轻化趋势,一直是严重威胁女性健康的疾病。越来越多的证据表明,微rna (miRNAs)和信使rna (mrna)在EEC发病的各种生物学过程中发挥着重要作用。本研究旨在确定与雌二醇调节的EEC相关的潜在预后生物标志物。方法分别用250 nM雌二醇(n = 3)、50 nM雌二醇(n = 3)和对照组(n = 3)处理子宫内膜癌Ishikawa细胞,从Cancer Genome Atlas数据库(n = 408)和原始测序中获得EEC的srna表达谱。TargetScan数据库用于预测预后相关差异表达miRNAs (DEMs)的靶基因。随后,对靶基因和差异表达mrna (DEGs)的重叠部分进行功能富集分析和拓扑分析。Kaplan-Meier分析用于预测与预后相关的靶基因,以鉴定预后生物标志物和细胞群景观;基于NCBI Sequence Read Archive数据库的单细胞转录组测序数据,进行基因表达分析,定位与预后相关的deg。结果4个与雌二醇相关的deg与预后相关,筛选出235个重叠的靶deg并纳入功能富集分析和蛋白-蛋白相互作用网络可视化研究。此外,通过生存分析,SACS和GPR157被确定为脑电图预后的潜在生物标志物。此外,对单细胞转录组数据进行了分析,以显示特定细胞类型中基因表达水平的变化。结论本研究表明,受雌二醇调控的miR-142-5p-SACS和miR-30a-5p-GPR157可能有望作为脑电图的诊断和预后生物标志物和新的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Clinics
Clinics 医学-医学:内科
CiteScore
4.10
自引率
3.70%
发文量
129
审稿时长
52 days
期刊介绍: CLINICS is an electronic journal that publishes peer-reviewed articles in continuous flow, of interest to clinicians and researchers in the medical sciences. CLINICS complies with the policies of funding agencies which request or require deposition of the published articles that they fund into publicly available databases. CLINICS supports the position of the International Committee of Medical Journal Editors (ICMJE) on trial registration.
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