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关于该基因与胃癌发生之间关联的分析

An Analysis Regarding the Association Between the Gene and Gastric Carcinogenesis.

作者信息

Li Shu, Zhao Wei, Sun Manyi

机构信息

Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China.

General Data Technology Co., Ltd., Tianjin, China.

出版信息

Front Genet. 2020 Jun 16;11:620. doi: 10.3389/fgene.2020.00620. eCollection 2020.

Abstract

For datasets of gastric cancer collected by TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus) repositories, we applied a bioinformatics approach to obtain expression data for the (immunoglobulin superfamily containing leucine-rich repeat) gene, which is highly expressed in gastric cancer tissues and closely associated with clinical prognosis. Although we did not observe an overall association of mutation, high expression or copy number variation with survival, hypomethylation of four methylated sites (assessed by the probes cg05195566, cg17258195, cg09664357, and cg07297039) of was negatively correlated with high expression levels of and was associated with poor clinical prognosis. In addition, we detected a correlation between expression and the infiltration levels of several immune cells, especially CD8 T cells, macrophages and dendritic cells. We also identified a series of genes that were positively and negatively correlated with expression based on the TCGA-STAD, GSE13861, and GSE29272 datasets. Principal component analysis and random forest analysis were employed to further screen for six hub genes, including , , , , , and , which exhibited a good ability to differentiate between tumor and normal samples. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway and gene set enrichment analysis data also suggested a potential relationship between gene expression and epithelial-mesenchymal transition (EMT). expression was negatively correlated with sensitivity to PX-12 and NSC632839. Taken together, these results show that the gene is involved in gastric carcinogenesis, and the underlying molecular mechanisms may include DNA methylation, EMT, and immune cell infiltration.

摘要

对于由TCGA(癌症基因组图谱)和GEO(基因表达综合数据库)库收集的胃癌数据集,我们应用生物信息学方法获取(含富亮氨酸重复序列的免疫球蛋白超家族)基因的表达数据,该基因在胃癌组织中高表达且与临床预后密切相关。尽管我们未观察到该基因突变、高表达或拷贝数变异与生存之间的总体关联,但该基因四个甲基化位点(由探针cg05195566、cg17258195、cg09664357和cg07297039评估)的低甲基化与该基因的高表达水平呈负相关,并与不良临床预后相关。此外,我们检测到该基因表达与几种免疫细胞的浸润水平之间存在相关性,尤其是CD8 T细胞、巨噬细胞和树突状细胞。我们还基于TCGA-STAD、GSE13861和GSE29272数据集鉴定了一系列与该基因表达呈正相关和负相关的基因。采用主成分分析和随机森林分析进一步筛选出六个枢纽基因,包括、、、、和,它们在区分肿瘤样本和正常样本方面表现出良好的能力。GO(基因本体论)和KEGG(京都基因与基因组百科全书)通路及基因集富集分析数据也表明该基因表达与上皮-间质转化(EMT)之间可能存在关系。该基因表达与对PX-12和NSC632839的敏感性呈负相关。综上所述,这些结果表明该基因参与胃癌发生,其潜在分子机制可能包括DNA甲基化、EMT和免疫细胞浸润。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/403f/7308588/6a46121bdc39/fgene-11-00620-g001.jpg

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