六价铬致肺上皮细胞恶性转化的关键基因筛选——基于GEO数据库

Key genes in malignant transformation of lung epithelial cells induced by hexavalent chromium based on GEO database

[背景]六价铬[Cr(Ⅵ)]能够诱导肺上皮细胞恶性转化,但其分子机制仍不十分明确。[目的]运用生物信息学分析方法挖掘Cr(Ⅵ)诱导肺上皮细胞恶性病变的关键基因并探讨其发生机制。[方法]从公共基因表达数据库(GEO)中下载与Cr(Ⅵ)毒效应相关的高通量基因表达谱数据,通过对各数据集中差异表达基因取交集获得共表达的差异表达基因;利用DAVID 6.8软件对所选择的差异表达基因进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)信号通路分析;采用STRING数据库和Cytoscape 3.8.2构建蛋白质相互作用集合并进行可视化分析;借助GEPIA2在线分析工具得到核心基因(Hub基因)在肺癌中的表达情况。[结果]筛选出GSE24025和GSE36684数据集中差异共表达的差异表达基因共234个,其中上调基因99个,下调基因135个。GO及KEGG分析结果主要富集在细胞黏附、负调节细胞增殖及转录失调等条目。基于STRING数据库生成蛋白相互作用(PPI)集合,经Cytoscape软件筛选出4个得分较高的功能模块和6个Hub基因,其中FBLN1在肺部各亚型肿瘤中的表达趋势均与表达谱筛选的结果一致。[结论] Cr(Ⅵ)染毒引起肺上皮细胞多个基因的差异表达,涉及细胞形态、运动、生存及与癌症相关的表型功能和信号通路受到影响。FBLN1可能是细胞恶性病变的核心基因。

[Background] Hexavalent chromium [Cr(Ⅵ)] can induce malignant transformation of lung epithelial cells, but its molecular mechanism is still unclear.[Objective] This study aims to explore the key genes of Cr(Ⅵ)-induced malignant transformation of lung epithelial cells and the mechanism of the transformation by bioinformatics analysis.[Methods] High-throughput gene expression profile data related to Cr(Ⅵ)-induced toxic effect was downloaded from the Gene Expression Omnibus(GEO) database, and the co-expressed genes were obtained by the intersection of differentially expressed genes in each dataset. DAVID6.8 was used to analyze the function enrichment of gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathways of the selected differential expression genes. STRING,and Cytoscape 3.8.2 were applied to construct and visualize the protein-protein interaction network. The expressions of Hub genes in lung tumor were obtained by GEPIA2.[Results] A total of 234 differentially expressed genes were screened out from the GSE24025 and GSE36684 datasets, among which 99 genes were up-regulated while 135 genes were downregulated. The results of GO and KEGG analyse were mainly concentrated in cell adhesion,negative regulation of cell proliferation, and transcription disorders. A rotein-protein interaction network was generated by STRING database and Cytoscape software. Four functional modules with high scores and 6 Hub genes were finally retrieved. The expression trend of FBLN1 in lung cancer subtypes was consistent with the results of transcriptome screening.[Conclusion] Cr(Ⅵ) exposure causes the differential expression of multiple genes in lung epithelial cells, involving cell morphology,movement, survival fate, phenotype function and signal pathway related to cancer development. FBLN1 may be the critical gene related to malignant cytopathy.