本文選題：基因表達(dá)譜 + 胚胎干細(xì)胞　； 參考：《浙江理工大學(xué)》2017年碩士論文

【摘要】：癌癥干細(xì)胞假說(shuō)認(rèn)為癌癥干細(xì)胞是癌癥異常增殖、侵襲、轉(zhuǎn)移、耐藥以及復(fù)發(fā)等的根源。本文基于這個(gè)假說(shuō),分析四種癌癥的基因和miRNAs混合表達(dá)數(shù)據(jù),挖掘與癌癥干細(xì)胞相關(guān)的關(guān)鍵調(diào)控基因。首先本研究利用分類算法將746個(gè)乳腺癌樣本中的18409個(gè)基因和1035個(gè)miRNAs劃分到不同的共表達(dá)模塊中;并與胚胎干細(xì)胞和間充質(zhì)干細(xì)胞的相關(guān)數(shù)據(jù)庫(kù)做富集度分析,得到兩個(gè)大小分別為2019和859且與上述兩類干細(xì)胞相關(guān)的基因集。另外對(duì)膠質(zhì)母細(xì)胞瘤、低等級(jí)的腦膠質(zhì)瘤和肺癌的混合表達(dá)數(shù)據(jù)重復(fù)上述過(guò)程,最終得到178個(gè)與胚胎干細(xì)胞相關(guān)的基因和7個(gè)與間充質(zhì)干細(xì)胞相關(guān)的基因。其次通過(guò)比對(duì)這兩個(gè)基因集在GSE29625和GSE28974數(shù)據(jù)中的表達(dá)方式,進(jìn)一步驗(yàn)證了兩個(gè)基因集與兩類干細(xì)胞的相關(guān)性。另外發(fā)現(xiàn)由178個(gè)基因組成的與胚胎干細(xì)胞相關(guān)的基因集參與由轉(zhuǎn)錄因子E2F介導(dǎo)的轉(zhuǎn)錄過(guò)程。最后通過(guò)構(gòu)建這兩個(gè)基因集的調(diào)控網(wǎng)絡(luò),在乳腺癌中篩選出兩個(gè)胚胎干細(xì)胞的特異性關(guān)鍵基因TPX2和MCM10,以及間充質(zhì)干細(xì)胞的特異基因COL5A2。并通過(guò)查看178個(gè)與胚胎干細(xì)胞相關(guān)的重復(fù)基因在四種癌癥調(diào)控網(wǎng)絡(luò)中的頂點(diǎn)出度,篩選出兩個(gè)關(guān)鍵調(diào)控基因BUB1B和NCAPH。這些基因可以作為治療乳腺癌的潛在的標(biāo)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.
【學(xué)位授予單位】：浙江理工大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R73-3

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