以上皮細胞間質化與增生相關功能來描述癌症幹細胞之基因型

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姓名

許爵麟(Chueh-Lin Hsu) 查詢紙本館藏

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系統生物與生物資訊研究所

論文名稱

以上皮細胞間質化與增生相關功能來描述癌症幹細胞之基因型
(Genotypes of cancer stem cells characterized by epithelial-to-mesenchymal transition and proliferation related functions)

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摘要(中)

癌幹細胞或稱為具有幹細胞特性的癌細胞，通常表現耐藥性，以及高效率誘導癌症的能力。在過去幾年，公共資料庫收集的全基因組表現量數據，已有癌幹細胞分子與功能特徵的相關研究，這些材料足夠提供進一步的分析。在這裡，本研究使用公開的癌幹細胞全基因組基因表現量數據集，利用主成分分析篩選出十四組癌幹細胞組和四組控制組的高品質數據集。使用來自分子簽名資料庫的6,002個基因分子簽名，分析這十八組數據集。癌幹細胞數據集在本研究被區分為三種基因型。第一型由神經膠質瘤癌幹細胞主導，明顯強化增生相關功能，同時抑制上皮細胞間質化相關功能。第二型皆為乳癌幹細胞組成，顯著增強上皮細胞間質化相關功能，但無增生相關功能的反應。第三型由卵巢癌、前列腺癌、大腸癌的癌幹細胞所組成，有同時顯著抑制增生與上皮細胞間質化相關功能的錯雜現象。

摘要(英)

Cancer stem cells (CSCs), or cancer cells with stem cell-like properties, generally exhibit drug resistance and have highly potent cancer inducing capabilities. Genome-wide expression data collected at public repositories over the last few years provide excellent material for studies that can lead to insights concerning the molecular and functional characteristics of CSCs. Here, we conducted functional genomic studies of CSC based on fourteen PCA-screened high quality public CSC whole genome gene expression datasets and, as control, four high quality non-stem-like cancer cell and non-cancerous stem cell datasets from the Gene Expression Omnibus database. A total of 6,002 molecular signatures were taken from the Molecular Signatures Database and used to characterize the datasets, which, under two-way hierarchical clustering, formed three genotypes. Type 1, consisting of mainly glia CSCs, had significantly enhanced proliferation, and significantly suppressed epithelial-mesenchymal transition (EMT), related functions. Type 2, mainly breast CSCs, had significantly enhanced EMT, but not proliferation, related functions. Type 3, composed of ovarian, prostate, and colon CSCs, had significantly suppressed proliferation related functions and mixed expressions on EMT related functions.

關鍵字(中)

★ 癌症幹細胞
★ 上皮細胞間質化
★ 增生

關鍵字(英)

★ cancer stem cell
★ epithelial-mesenchymal transition
★ EMT
★ proliferation
★ GSEA

論文目次

圖目錄 iv
表目錄 vi
一、介紹 1
1.1 癌幹細胞（cancer stem cells） 1
1.2 增生（proliferation） 2
1.3 上皮細胞間質化（epithelial to mesenchymal transitions） 4
1.4 辨識癌幹細胞 6
1.5 微陣列（microarray） 8
1.6 基因本體論（gene ontology） 9
1.7 研究問題 10
二、材料與方法 11
2.1 癌幹細胞數據集的收集 11
2.2 分子簽名資料庫（MSigDB） 12
2.3 主成分分析（PCA）的質量控制 12
2.4 基於個別基因的分析（individual gene-based analysis） 13
2.5 基於基因集的分析（gene set-based analysis） 14
2.6 基因與簽名的挑選 15
2.7 單向和雙向的集群分析 16
2.8 集群基因集（cluster gene set）的建立 16
2.9 數據集分類的驗證 16
2.10 特定基因型的CSCs差異基因挑選 17
2.11 基因本體論（gene ontology）和京都基因與基因組百科全書（kyoto encyclopedia of genes and genomes）的富集分析 18
三、結果 19
3.1 挑選具有高PCA分數的數據集與差異表現量基因 19
3.2 數據組在IGA的DEGs交集 21
3.3 優於IGA的GSA單向集群分類 22
3.4 GSA產生三種簽名集群和三種基因型 24
3.5 使用CGSs構建集群熱圖 26
3.6 六個已知癌症和幹細胞相關簽名集群與152個簽名集群的結果類似 28
3.7 三個CGSs在GO術語中的富集強度 29
3.8 具有增生與EMT相關功能特徵的基因型群組 31
四、討論 37
五、總結 42
參考文獻 43
附表一、專有名詞縮寫對照表 48

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指導教授

李弘謙(Hoong-Chien Lee)

審核日期

2017-1-23

推文