基于转录组学探讨骨肉瘤关键基因与相关通路△

Identification of key genes and related pathways in osteosarcoma based on transcriptomics

摘要:

[目的] 通过转录组测序和生物信息学分析寻找骨肉瘤发生的关键基因和相关通路。[方法] 收集骨肉瘤组织和癌旁对照组织，通过转录组芯片建立表达谱并筛选差异性表达基因（differentially expressed genes, DEGs）。利用在线数据库对DEGs进行基因本体（gene ontology, GO） 和京都基因与基因组百科全书（kyoto encyclopedia of genes and genomes, KEGG） 富集分析。[结果] 本研究共纳入5 对骨肉瘤和癌旁对照组织，共筛选出1 211 个在肿瘤组织中表达显著上调和810 个显著下调的基因。表达量上调最多的5 个基因依次为COL1A1 （collagen type I alpha 1 chain）、SPP1 （secreted phosphoprotein 1）、POSTN （periostin）、TYMS（thymidylate synthetase） 和TNC（tenascin C）；表达量下调最多的5 个基因依次为ATP1A2（ATPase, Na+/K+ transporting,alpha 2 polypeptide）、PDK4（pyruvate dehydrogenase kinase, isozyme 4）、CLIC5（chloride intracellular channel 5）、ACTA1（actin, al-pha 1, skeletal muscle） 和FABP4（fatty acid binding protein 4）。GO 富集分析提示DEGs 主要富集于组织发育、小分子代谢过程和细胞周期等生物过程，KEGG 富集分析提示DEGs 主要涉及黏着斑、细胞外基质受体相互作用、癌症信号通路和细胞周期相关通路。[结论] COL1A1、SPP1、POSTN、TYMS、TNC、ATP1A2、PDK4、CLIC5、ACTA1 和FABP4 基因可能在骨肉瘤的发生发展中起重要调控作用。

Abstract:

[Objective] Transcriptome sequencing and bioinformatics analysis were used to identify key genes and related pathways inosteosarcoma. [Methods] The osteosarcoma tissues and adjacent control tissues were collected to analyze the expression profiles by tran-scriptome microarray and differential expression genes (DEGs). The Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis of DEGs was performed through online database. [Results] A total of 5 pairs of osteosarcoma and para-tumorcontrol tissues were included in this study. A total of 1 211 genes with significantly up-regulated expression and 810 significantly down-reg-ulated expression were screened in tumor tissues. GO analysis suggested that DEGs was mainly concentrated in biological processes such astissue development, small molecule metabolism and cell cycle, while KEGG analysis suggested that DEGs was mainly involved in adhesionplaques, extracellular matrix receptor interactions, cancer signaling pathways and cell cycle related pathways. [Conclusion] COL1A1, SPP1,POSTN, TYMS, TNC, ATP1A2, PDK4, CLIC5, ACTA1 and FABP4 may play an important role in the development of osteosarcoma.