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胃癌相关基因特征的预后价值:基于综合生物信息学方法的荟萃分析证据。

Prognostic value of gastric cancer-associated gene signatures: Evidence based on a meta-analysis using integrated bioinformatics methods.

机构信息

Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Heping District, Shenyang, China.

出版信息

J Cell Mol Med. 2018 Nov;22(11):5743-5747. doi: 10.1111/jcmm.13823. Epub 2018 Aug 22.

Abstract

Selecting differentially expressed genes (DEGs) based on integrated bioinformatics analyses has been used in previous studies to explore potential biomarkers in gastric cancer (GC) with microarray and RNA sequencing data. However, the genes obtained may be inaccurate because of noisy data and errors, as well as insufficient clinical sample sizes. Thus, we aimed to find robust and strong DEGs with prognostic value for GC, where the robust rank aggregation method was employed to select significant DEGs from eight Gene Expression Omnibus data sets with a total of 140 up-regulated and 206 down-regulated genes. Network data mining was then used to screen hub genes, and 11 genes were filtered using Fisher's exact test. Based on these results, we built a prognostic signature with seven genes (FBN1, MMP1, PLAU, SPARC, COL1A2, COL2A1 and ATP4A) using stepwise multivariate Cox proportional hazard regression. According to the risk score for each patient, we found that high-risk group patients had significantly worse survival results compared with those in the low-risk group (log-rank test P-value < 0.001). This seven-gene signature was then validated with an external data set. Thus, we established a signature based on seven DEGs with prognostic value for GC patients using multi-steps bioinformatics methods, which may provide novel insights and potential biomarkers for prognosis, as well as possibly serving as new therapeutic targets in clinical applications.

摘要

基于整合生物信息学分析选择差异表达基因(DEGs)已被用于先前的研究中,以利用微阵列和 RNA 测序数据探索胃癌(GC)中的潜在生物标志物。然而,由于数据噪声和误差以及临床样本量不足,获得的基因可能不够准确。因此,我们旨在寻找具有 GC 预后价值的稳健且强的 DEGs,其中采用稳健秩聚合方法从 8 个 Gene Expression Omnibus 数据集(共 140 个上调和 206 个下调基因)中选择显著的 DEGs。然后进行网络数据挖掘以筛选枢纽基因,并使用 Fisher 精确检验过滤 11 个基因。基于这些结果,我们使用逐步多变量 Cox 比例风险回归构建了一个包含 7 个基因(FBN1、MMP1、PLAU、SPARC、COL1A2、COL2A1 和 ATP4A)的预后特征。根据每位患者的风险评分,我们发现高危组患者的生存结果明显差于低危组(对数秩检验 P 值<0.001)。然后,我们使用外部数据集对该七基因签名进行了验证。因此,我们使用多步骤生物信息学方法建立了一个具有 GC 患者预后价值的基于七个 DEGs 的特征,这可能为预后提供新的见解和潜在的生物标志物,并可能在临床应用中作为新的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdd5/6201382/5a881d8e3ef0/JCMM-22-5743-g001.jpg

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