基于基因表达谱的癌症干细胞调控基因的识别研究

发布时间：2018-06-13 05:33

本文选题：基因表达谱 + 胚胎干细胞　；参考：《浙江理工大学》2017年硕士论文

【摘要】：癌症干细胞假说认为癌症干细胞是癌症异常增殖、侵袭、转移、耐药以及复发等的根源。本文基于这个假说,分析四种癌症的基因和miRNAs混合表达数据,挖掘与癌症干细胞相关的关键调控基因。首先本研究利用分类算法将746个乳腺癌样本中的18409个基因和1035个miRNAs划分到不同的共表达模块中;并与胚胎干细胞和间充质干细胞的相关数据库做富集度分析,得到两个大小分别为2019和859且与上述两类干细胞相关的基因集。另外对胶质母细胞瘤、低等级的脑胶质瘤和肺癌的混合表达数据重复上述过程,最终得到178个与胚胎干细胞相关的基因和7个与间充质干细胞相关的基因。其次通过比对这两个基因集在GSE29625和GSE28974数据中的表达方式,进一步验证了两个基因集与两类干细胞的相关性。另外发现由178个基因组成的与胚胎干细胞相关的基因集参与由转录因子E2F介导的转录过程。最后通过构建这两个基因集的调控网络,在乳腺癌中筛选出两个胚胎干细胞的特异性关键基因TPX2和MCM10,以及间充质干细胞的特异基因COL5A2。并通过查看178个与胚胎干细胞相关的重复基因在四种癌症调控网络中的顶点出度,筛选出两个关键调控基因BUB1B和NCAPH。这些基因可以作为治疗乳腺癌的潜在的标靶基因。
[Abstract]:The cancer stem cell hypothesis suggests that cancer stem cells are the cause of abnormal proliferation, invasion, metastasis, drug resistance, and recurrence of cancer. Based on this hypothesis, the mixed expression data of four kinds of cancer genes and miRNAs were analyzed, and the key regulatory genes related to cancer stem cells were excavated. First of all, 18409 genes and 1035 miRNAs of 746 breast cancer samples were divided into different coexpression modules by classification algorithm, and the enrichment degree was analyzed with the relevant databases of embryonic stem cells and mesenchymal stem cells. Two sets of genes, 2019 and 859, were obtained and related to the above two types of stem cells. In addition, the mixed expression data of glioblastoma, low grade glioma and lung cancer were repeated. Finally, 178 genes related to embryonic stem cells and 7 genes related to mesenchymal stem cells were obtained. Secondly, by comparing the expression of these two gene sets in GSE29625 and GSE28974 data, the correlation between the two gene sets and two types of stem cells was further verified. In addition, a set of 178 genes related to embryonic stem cells was found to be involved in the transcription process mediated by transcription factor E2F. Finally, by constructing the regulatory network of these two sets of genes, two specific key genes TPX2 and MCM10 of embryonic stem cells and COL5A2 of mesenchymal stem cells were screened from breast cancer. Two key regulatory genes, BUB1B and NCAPH, were screened by examining the vertices of 178 repeat genes associated with embryonic stem cells in four cancer regulatory networks. These genes can be used as potential target genes for the treatment of breast cancer.
【学位授予单位】：浙江理工大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R73-3

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