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一种基于七种免疫相关 RNA 的新型预后预测模型,用于预测早期宫颈鳞状细胞癌患者的总生存率。

A novel prognostic prediction model based on seven immune-related RNAs for predicting overall survival of patients in early cervical squamous cell carcinoma.

机构信息

Department of Obstetrics and Gynecology, The Third Hospital of Jilin University, No 126, Xiantai Street, Changchun, Jilin, 130033, People's Republic of China.

出版信息

BMC Med Genomics. 2021 Feb 15;14(1):49. doi: 10.1186/s12920-021-00885-3.

Abstract

BACKGROUND

In this study, we aimed to mine immune-related RNAs expressed in early cervical squamous cell carcinoma to construct prognostic prediction models.

METHODS

The RNA sequencing data of 309 cervical squamous cell carcinoma (CSCC) cases, including data of individuals with available clinical information, were obtained from The Cancer Genome Atlas (TCGA) database. We included 181 early-stage CSCC tumor samples with clinical survival and prognosis information (training dataset). Then, we downloaded the GSE44001 gene expression profile data from the National Center for Biotechnology Information Gene Expression Omnibus (validation dataset). Gene ontology annotation and the Kyoto Encyclopedia of Genes and Genomes pathway analyses were used to analyze the biological functions of differentially expressed immune-related genes (DEIRGs). We established protein-protein interactions and competing endogenous RNA networks using Cytoscape. Using the Kaplan-Meier method, we evaluated the association between the high- and low-risk groups and the actual survival and prognosis information. Our univariate and multivariate Cox regression analyses screened for independent prognostic factors.

RESULTS

We identified seven prognosis-related signature genes (RBAKDN, CXCL2, ZAP70, CLEC2D, CD27, KLRB1, VCAM1), the expression of which was markedly associated with overall survival (OS) in CSCC patients. Also, the risk score of the seven-gene signature discripted superior ability to categorize CSCC patients into high-risk and low-risk groups, with a observablydifferent OS in the training and validation datasets. We screened two independent prognostic factors (Pathologic N and prognostic score model status) that correlated significantly by univariate and multivariate Cox regression analyses in the TCGA dataset. To further explore the potential mechanism of immune-related genes, we observed associated essential high-risk genes with a cytokine-cytokine receptor interaction.

CONCLUSIONS

This study established an immune-related RNA signature, which provided a reliable prognostic tool and may be of great significance for determining immune-related biomarkers in CSCC.

摘要

背景

本研究旨在挖掘早期宫颈鳞状细胞癌中表达的免疫相关 RNA,构建预后预测模型。

方法

从癌症基因组图谱(TCGA)数据库中获取了 309 例宫颈鳞状细胞癌(CSCC)病例的 RNA 测序数据,包括具有可用临床信息的个体数据。我们纳入了 181 例具有临床生存和预后信息的早期 CSCC 肿瘤样本(训练数据集)。然后,我们从国家生物技术信息中心基因表达综合数据库(验证数据集)下载了 GSE44001 基因表达谱数据。使用基因本体注释和京都基因与基因组百科全书通路分析来分析差异表达的免疫相关基因(DEIRGs)的生物学功能。我们使用 Cytoscape 构建了蛋白质-蛋白质相互作用和竞争性内源性 RNA 网络。使用 Kaplan-Meier 方法评估高风险组和低风险组与实际生存和预后信息的相关性。我们的单变量和多变量 Cox 回归分析筛选了独立的预后因素。

结果

我们确定了七个与预后相关的特征基因(RBAKDN、CXCL2、ZAP70、CLEC2D、CD27、KLRB1、VCAM1),其表达与 CSCC 患者的总生存率(OS)显著相关。此外,七个基因特征的风险评分能够很好地区分 CSCC 患者的高风险组和低风险组,在训练和验证数据集的 OS 中具有明显差异。我们通过单变量和多变量 Cox 回归分析在 TCGA 数据集中筛选出两个与预后显著相关的独立预后因素(病理 N 和预后评分模型状态)。为了进一步探讨免疫相关基因的潜在机制,我们观察到与关键高风险基因相关的细胞因子-细胞因子受体相互作用。

结论

本研究建立了一个免疫相关的 RNA 特征,为 CSCC 提供了一个可靠的预后工具,可能对确定 CSCC 中的免疫相关生物标志物具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5587/7885601/4af9318eae75/12920_2021_885_Fig1_HTML.jpg

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