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子宫内膜癌中ceRNA网络的综合分析:预后及治疗意义

Comprehensive analysis of ceRNA Networks in UCEC: Prognostic and therapeutic implications.

作者信息

Fan Li, Lan Mengqiu, Wei Xiaohua, Wei Lili, Yang Liuhong, Nong Liuying, Wei Jiajia, Li Jingjing, Huang Wenjie

机构信息

Department of Reproductive Medicine, Guangzhou Women and Children's Medical center Liuzhou Hospital, Liuzhou, Guangxi, China.

Reproductive Medicine Center, Liuzhou Maternity and Child Health Care Hospital, Liuzhou, China.

出版信息

PLoS One. 2025 Jan 30;20(1):e0314314. doi: 10.1371/journal.pone.0314314. eCollection 2025.

Abstract

Endometrial cancer (UCEC) is the most prevalent gynecological malignancy in high-income countries, and its incidence is rising globally. Although early-stage UCEC can be treated with surgery, advanced cases have a poor prognosis, highlighting the need for effective molecular biomarkers to improve diagnosis and prognosis. In this study, we analyzed mRNA and miRNA sequencing data from UCEC tissues and adjacent non-cancerous tissues from the TCGA database. Differential expression analysis was conducted using the DESeq2 package, identifying differentially expressed lncRNAs, miRNAs, and mRNAs (DElncRNAs, DEmiRNAs, and DEmRNAs). Key molecules were screened using LASSO regression, and a ceRNA network was constructed by predicting lncRNA-miRNA and miRNA-mRNA interaction, which were visualized with Cytoscape. Functional enrichment analysis elucidated the roles and mechanisms of the network. The prognostic potential of the identified RNAs was assessed through survival and Cox regression analyses, while methylation and immune infiltration analyses explored regulatory mechanisms and immune interactions. We identified a prognostic lncRNA-miRNA-mRNA ceRNA network in UCEC, centered on the CDKN2B-AS1-hsa-miR-497-5p-IGF2BP3 axis. Survival analyses confirmed the prognostic significance of this network, with univariate Cox regression demonstrating a strong association between its aberrant expression and overall prognosis in UCEC. However, multivariate Cox regression suggested that other clinical factors may modulate this relationship. Methylation analysis revealed low methylation levels of IGF2BP3, possibly contributing to its overexpression. Furthermore, immune infiltration studies highlighted significant correlations between CDKN2B-AS1, IGF2BP3, and multiple immune cell types, suggesting that this axis regulates the tumor immune microenvironment. These findings suggest that the CDKN2B-AS1-hsa-miR-497-5p-IGF2BP3 axis is a key regulatory element in UCEC and a potential therapeutic target.

摘要

子宫内膜癌(UCEC)是高收入国家中最常见的妇科恶性肿瘤,且其全球发病率正在上升。尽管早期UCEC可通过手术治疗,但晚期病例预后较差,这凸显了需要有效的分子生物标志物来改善诊断和预后。在本研究中,我们分析了来自TCGA数据库的UCEC组织和相邻非癌组织的mRNA和miRNA测序数据。使用DESeq2软件包进行差异表达分析,鉴定出差异表达的lncRNA、miRNA和mRNA(DElncRNA、DEmiRNA和DEmRNA)。使用LASSO回归筛选关键分子,并通过预测lncRNA-miRNA和miRNA-mRNA相互作用构建ceRNA网络,并用Cytoscape进行可视化。功能富集分析阐明了该网络的作用和机制。通过生存分析和Cox回归分析评估所鉴定RNA的预后潜力,同时甲基化和免疫浸润分析探索调控机制和免疫相互作用。我们在UCEC中鉴定出一个以CDKN2B-AS1-hsa-miR-497-5p-IGF2BP3轴为中心的预后lncRNA-miRNA-mRNA ceRNA网络。生存分析证实了该网络的预后意义,单变量Cox回归表明其异常表达与UCEC的总体预后之间存在强烈关联。然而,多变量Cox回归表明其他临床因素可能调节这种关系。甲基化分析显示IGF2BP3的甲基化水平较低,这可能导致其过表达。此外,免疫浸润研究突出了CDKN2B-AS1、IGF2BP3与多种免疫细胞类型之间的显著相关性,表明该轴调节肿瘤免疫微环境。这些发现表明CDKN2B-AS1-hsa-miR-497-5p-IGF2BP3轴是UCEC中的关键调控元件和潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e00/11781699/2b95f8286f22/pone.0314314.g001.jpg

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