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子宫体子宫内膜癌lncRNA介导的ceRNA网络的综合生物信息学分析

Comprehensive bioinformatic analyses of lncRNA-mediated ceRNA network for uterine corpus endometrial carcinoma.

作者信息

Cai Yiran, Cui Jin, Wang Zhisu, Wu Huiqun

机构信息

Medical School of Nantong University, Nantong, China.

Department of Medical Informatics, Medical School of Nantong University, Nantong, China.

出版信息

Transl Cancer Res. 2022 Jul;11(7):1994-2012. doi: 10.21037/tcr-22-249.

Abstract

BACKGROUND

Given that long non-coding RNAs (lncRNAs) involved in the tumor initiation or progression of the endometrium and that competing endogenous RNA (ceRNA) plays an important role in increasingly more biological processes, lncRNA-mediated ceRNA is likely to function in the pathogenesis of uterine corpus endometrial carcinoma (UCEC). Our present study aimed to explore the potential molecular mechanisms for the prognosis of UCEC through a lncRNA-mediated ceRNA network.

METHODS

The transcriptome profiles and corresponding clinical profiles of UCEC dataset were retrieved from Clinical Proteomic Tumor Analysis Consortium (CPTAC) and The Cancer Genome Atlas (TCGA) databases respectively. Differentially expressed genes (DEGs) in UCEC samples were identified via "Edge R" package. Then, an integrated bioinformatics analysis including functional enrichment analysis, tumor infiltrating immune cell (TIIC) analysis, Kaplan-Meier curve, Cox regression analysis were conducted to analyze the prognostic biomarkers.

RESULTS

In the CPTAC dataset of UCEC, a ceRNA network comprised of 36 miRNAs, 123 lncRNAs and 124 targeted mRNAs was established, and 8 of 123 prognostic-related Differentially Expressed long noncoding RNAs (DElncRNAs) were identified. While in the TCGA dataset, a ceRNA network comprised of 38 miRNAs, 83 lncRNAs and 110 targeted mRNAs was established, and 2 of 83 prognostic-related DElncRNAs were identified. After filtered by risk grouping and Cox regression analysis, 10 prognostic-related lncRNAs including LINC00443, LINC00483, C2orf48, TRBV11-2, MEG-8 were identified. In addition, 33 survival-related Differentially Expressed messenger RNA (DEmRNAs) in two ceRNA networks were further validated in the Human Protein Atlas Portal (HPA) database. Finally, six lncRNA/miRNA/mRNA axes were established to elucidate prognostic regulatory roles in UCEC.

CONCLUSIONS

Several prognostic lncRNAs are identified and prognostic model of lncRNA-mediated ceRNA network is constructed, which promotes the understanding of UCEC development mechanisms and potential therapeutic targets.

摘要

背景

鉴于长链非编码RNA(lncRNAs)参与子宫内膜肿瘤的发生或进展,且竞争性内源RNA(ceRNA)在越来越多的生物学过程中发挥重要作用,lncRNA介导的ceRNA可能在子宫体子宫内膜癌(UCEC)的发病机制中发挥作用。我们目前的研究旨在通过lncRNA介导的ceRNA网络探索UCEC预后的潜在分子机制。

方法

分别从临床蛋白质组肿瘤分析联盟(CPTAC)和癌症基因组图谱(TCGA)数据库中检索UCEC数据集的转录组谱和相应的临床谱。通过“Edge R”软件包鉴定UCEC样本中的差异表达基因(DEGs)。然后,进行包括功能富集分析、肿瘤浸润免疫细胞(TIIC)分析、Kaplan-Meier曲线、Cox回归分析在内的综合生物信息学分析,以分析预后生物标志物。

结果

在UCEC的CPTAC数据集中,建立了一个由36个miRNA、123个lncRNA和124个靶向mRNA组成的ceRNA网络,并鉴定出123个与预后相关的差异表达长链非编码RNA(DElncRNAs)中的8个。而在TCGA数据集中,建立了一个由38个miRNA、83个lncRNA和110个靶向mRNA组成的ceRNA网络,并鉴定出83个与预后相关的DElncRNAs中的2个。经过风险分组和Cox回归分析筛选,鉴定出10个与预后相关的lncRNA,包括LINC00443、LINC00483、C2orf48、TRBV11-2、MEG-8。此外,在人类蛋白质图谱门户(HPA)数据库中进一步验证了两个ceRNA网络中33个与生存相关的差异表达信使RNA(DEmRNAs)。最后,建立了六个lncRNA/miRNA/mRNA轴,以阐明其在UCEC中的预后调节作用。

结论

鉴定出了几种与预后相关的lncRNA,并构建了lncRNA介导的ceRNA网络的预后模型,这有助于深入了解UCEC的发生机制和潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1ed/9372196/71785435d08e/tcr-11-07-1994-f1.jpg

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