An Analysis Regarding the Association Between the ISLR Gene and Gastric Carcinogenesis
An Analysis Regarding the Association Between the ISLR Gene and Gastric Carcinogenesis
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DOI：
10.3389/fgene.2020.00620
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发表时间：
2020-06-16
影响因子：
3.7
通讯作者：
Sun, Manyi
中科院分区：
文献类型：
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作者：
Li, Shu;Zhao, Wei;Sun, Manyi
针对TCGA（The Cancer Genome Atlas）和GEO（Gene Expression Omnibus）数据库收集的胃癌数据集，采用生物信息学方法获得了ISLR（immunoglobulin superfamily containing leucine-rich repeat）基因的表达数据。ISLR基因在胃癌组织中高表达，与临床预后密切相关。虽然我们没有观察到ISLR突变、高表达或拷贝数变异与生存率的总体相关性，但ISLR四个甲基化位点的低甲基化（通过探针cg 05195566、cg 17258195、cg 09664357和cg 07297039评估）与ISLR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ISLR表达与多种免疫细胞（尤其是CD 8（+）T细胞、巨噬细胞和树突状细胞）的浸润水平之间存在相关性。我们还基于TCGA-STAD、GSE 13861和GSE 29272数据集鉴定了一系列与ISLR表达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6个具有良好区分肿瘤和正常组织的功能的枢纽基因，包括ISLR、COL 1A 2、CDH 11、CDH、COL 3A 1和COL 1A 1。GO（Gene Ontology）和KEGG（京都基因和基因组百科全书）途径和基因集富集分析数据也提示ISLR基因表达与上皮-间质转化（EMT）之间存在潜在的关系，ISLR表达与对PX-12和NSC 632839的敏感性呈负相关。综上所述，这些结果表明ISLR基因参与胃癌的发生，其潜在的分子机制可能包括DNA甲基化、EMT和免疫细胞浸润。
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 theISLR(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 ofISLRmutation, high expression or copy number variation with survival, hypomethylation of four methylated sites (assessed by the probes cg05195566, cg17258195, cg09664357, and cg07297039) ofISLRwas negatively correlated with high expression levels ofISLRand was associated with poor clinical prognosis. In addition, we detected a correlation betweenISLRexpression 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 withISLRexpression 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, includingISLR,COL1A2,CDH11,SPARC,COL3A1, andCOL1A1, 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 betweenISLRgene expression and epithelial-mesenchymal transition (EMT).ISLRexpression was negatively correlated with sensitivity to PX-12 and NSC632839. Taken together, these results show that theISLRgene is involved in gastric carcinogenesis, and the underlying molecular mechanisms may include DNA methylation, EMT, and immune cell infiltration.