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胃癌中免疫微环境相关的竞争性内源RNA调控轴的综合分析

Integrative analysis of immune microenvironment-related CeRNA regulatory axis in gastric cancer.

作者信息

Chen Jie, Chen Jing Gui, Sun Bo, Wu Jiang Hong, Du Chun Yan

机构信息

Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.

出版信息

Math Biosci Eng. 2020 Jun 1;17(4):3953-3971. doi: 10.3934/mbe.2020219.

Abstract

This study aimed to identify significant immune microenvironment-related competing endogenous RNA (CeRNA) regulatory axis in gastric cancer (GC). Analysis of differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs), and lncRNAs (DElncRNAs) was performed for the microarray datasets. After abundance analysis of immune cell's infiltration, immune-related mRNAs and lncRNAs were obtained. Meanwhile, according to the Pearson correlation coefficient between immune-related mRNAs and lncRNAs, the co-expression mRNA-lncRNA pairs were screened. Furthermore, the target genes of co-existance miRNAs were predicted, and miRNA-lncRNA pairs were identified. Finally, the lncRNA-miRNA and miRNA-mRNA relationship regulated by the same miRNA was screened. Combining with the co-expression relationship between lncRNA and mRNA, the CeRNA network was constructed. In abundance analysis of immune cell's infiltration, a total of eight immune cells were obtained, in addition, 83 immune-related DElncRNAs and 705 immune-related DEmRNAs were screened. KEGG pathway enrichment analysis showed that these mRNAs were mainly involved in PI3K-Akt signaling pathway and human papillomavirus infection, while lncRNA were relevant to gastric acid secretion. A total of 25 miRNAs were significantly associated with immune-related mRNAs, such as hsa-miR-148a-3p, hsa-miR-17-5p, and hsa-miR-25-3p. From the mRNA-miRNA-lncRNA CeRNA network, we observed that AC104389.28─miR-17-5─SMAD5 axis and LINC01133─miR-17-5p─PBLD axis played a crucial role in the development of GC. Furthermore, resting memory CD4 T cells and plasma cells were closely associated with the pathogenesis of GC, and these immune cells might be affected by the key genes. The present study identified key genes that associated with immune microenvironment in GC, providing potential molecular targets for immunotherapy of GC.

摘要

本研究旨在鉴定胃癌(GC)中与免疫微环境相关的重要竞争性内源RNA(CeRNA)调控轴。对微阵列数据集进行差异表达mRNA(DEmRNAs)、miRNA(DEmiRNAs)和lncRNA(DElncRNAs)分析。在对免疫细胞浸润进行丰度分析后,获得了免疫相关的mRNA和lncRNA。同时,根据免疫相关mRNA与lncRNA之间的Pearson相关系数,筛选出共表达的mRNA-lncRNA对。此外,预测了共存miRNA的靶基因,并鉴定了miRNA-lncRNA对。最后,筛选了由同一miRNA调控的lncRNA-miRNA和miRNA-mRNA关系。结合lncRNA与mRNA之间的共表达关系,构建了CeRNA网络。在免疫细胞浸润的丰度分析中,共获得了8种免疫细胞,此外,筛选出了83种免疫相关的DElncRNAs和705种免疫相关的DEmRNAs。KEGG通路富集分析表明,这些mRNA主要参与PI3K-Akt信号通路和人乳头瘤病毒感染,而lncRNA与胃酸分泌有关。共有25种miRNA与免疫相关mRNA显著相关,如hsa-miR-148a-3p、hsa-miR-17-5p和hsa-miR-25-3p。从mRNA-miRNA-lncRNA CeRNA网络中,我们观察到AC104389.28─miR-17-5─SMAD5轴和LINC01133─miR-17-5p─PBLD轴在GC的发生发展中起关键作用。此外,静息记忆CD4 T细胞和浆细胞与GC的发病机制密切相关,这些免疫细胞可能受关键基因的影响。本研究鉴定了GC中与免疫微环境相关的关键基因,为GC的免疫治疗提供了潜在的分子靶点。

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