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结直肠癌lncRNA-miRNA-mRNA调控网络构建及综合预后分析与肿瘤免疫细胞浸润

Construction and Comprehensive Prognostic Analysis of a lncRNA-miRNA-mRNA Regulatory Network and Tumor Immune Cell Infiltration in Colorectal Cancer.

作者信息

Guo Xiong, Liang Xiaolong, Wang Yujun, Cheng Anqi, Qin Chuan, Zhang Han, Wang Ziwei

机构信息

Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Department of Pathology, Daping Hospital, Army Military Medical University, Chongqing, China.

出版信息

Front Genet. 2021 Jul 1;12:652601. doi: 10.3389/fgene.2021.652601. eCollection 2021.

DOI:10.3389/fgene.2021.652601
PMID:34276767
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8281064/
Abstract

Colorectal cancer (CRC) is a malignant tumor with high morbidity and mortality worldwide. Recent studies have shown that long noncoding RNAs (lncRNAs) play an important role in almost all human tumors, including CRC. Competitive endogenous RNA (ceRNA) regulatory networks have become hot topics in cancer research. Tumor-infiltrating immune cells (TICs) have also been reported to be closely related to the survival and prognosis of CRC patients. In this study, we used the lncRNA-miRNA-mRNA regulatory network combined with tumor immune cell infiltration to predict the survival and prognosis of 598 CRC patients. First, we downloaded the lncRNA, mRNA, and miRNA transcriptome data of CRC patients from The Cancer Genome Atlas (TCGA) database and identified differentially expressed genes through "limma" package of R software. The ceRNA regulatory network was established by using the "GDCRNATools" R package. Then, univariate Cox analysis and least absolute shrinkage and selection operator analysis were performed to identify the optimal prognostic network nodes, including SRPX, UST, H19, SNHG7, hsa-miR-29b-3p, and TTYH3. Next, we analyzed the differences in 22 types of TICs between 58 normal subjects and 206 CRC patients and included memory CD4 T cells, dendritic cells and neutrophils in the construction of a prognostic model. Finally, we identified the relationship between the ceRNA prognostic model and the infiltrating immune cell prognostic model. In conclusion, we constructed two prognostic models that provide insights on the prognosis and treatment strategy of CRC.

摘要

结直肠癌(CRC)是一种在全球范围内发病率和死亡率都很高的恶性肿瘤。最近的研究表明,长链非编码RNA(lncRNA)在几乎所有人类肿瘤中都发挥着重要作用,包括结直肠癌。竞争性内源RNA(ceRNA)调控网络已成为癌症研究的热点话题。据报道,肿瘤浸润免疫细胞(TICs)也与CRC患者的生存和预后密切相关。在本研究中,我们使用lncRNA-miRNA-mRNA调控网络结合肿瘤免疫细胞浸润来预测598例CRC患者的生存和预后。首先,我们从癌症基因组图谱(TCGA)数据库下载了CRC患者的lncRNA、mRNA和miRNA转录组数据,并通过R软件的“limma”包识别差异表达基因。使用“GDCRNATools”R包建立ceRNA调控网络。然后,进行单变量Cox分析和最小绝对收缩和选择算子分析,以识别最佳预后网络节点,包括SRPX、UST、H19、SNHG7、hsa-miR-29b-3p和TTYH3。接下来,我们分析了58名正常受试者和206名CRC患者之间22种TICs的差异,并将记忆性CD4 T细胞、树突状细胞和中性粒细胞纳入预后模型的构建中。最后,我们确定了ceRNA预后模型与浸润免疫细胞预后模型之间的关系。总之,我们构建了两个预后模型,为CRC的预后和治疗策略提供了见解。

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