- 學位論文
大腸直腸癌病人中抑制癌症基因啟動子區域甲基化程度之研究
Studying the promoter hypermethylation status of tumor suppressor genes in colorectal cancer
摘要
結腸直腸癌是人類工業文明發展後所大量產生之癌化病變，對於台灣人民的威脅性，僅次於肺癌、肝癌、子宮頸癌及乳癌。由於癌化的病灶多由良性息肉及贅瘤中惡化，因此探求結腸直腸癌癌化病灶的標誌物（marker），以對此癌可做較為早期的偵測及監控非常重要。在此中，DLC-1基因（Deleted in Liver Cell gene）自從1998年後被發現在肝癌的演化上扮演重要的角色後，在許多其他的癌症上也發現此基因上位於promoter的CpG islands有過度甲基化的現象，推論DLC-1基因的過度甲基化是一種經由epigenetic modification調節細胞癌化的方式。而Endothelin type B receptor (EDNRB)基因在偶然中發現造成巨結腸症，是否其甲基化亦會造成結腸直腸癌亦可探求。另外14-3-3σ藉由造成G2/M時期停止以達到調控細胞週期的能力，也被認為會影響結腸直腸細胞癌化的表現。本篇研究利用甲基化專一性聚合酶連鎖反應證實了EDNRB、14-3-3σ及DLC-1基因其促進子區域在結腸直腸癌中有高度甲基化情形並且發現EDNRB基因促進子區域的甲基化與結腸直腸癌的病理分期、DLC-1基因促進子區域的甲基化與結腸直腸癌的偵測抗原--癌胚抗原（CEA）量呈現正相關。
並列摘要
Colorectal cancer is a cancer often followed by industrialization. It threatens the people in Taiwan, only followed by lung cancer, hepatoma, cervical cancer and breast cancer. Because colorectal cells frequently originate from benign polyps or adenoma, seeking the marker to detect the early phase of colorectal cancer is very important. Among all, deleted in liver cell (DLC-1) gene was found to play an important role in hepatoma in 1998, and after that hypermethylation on the promoter of the DLC-1 gene was found in many other cancers, suggesting that epigenetic modification is another way to control the carcinogenesis. Another gene, Endothelin type B receptor (EDNRB), was found to cause megacolon syndrome (Waardenburg syndrome) by accident while searching the cause of white spot in mouse, and was also found hypermethylation on its promoter in some cancer cells. Whether promoter-hypermethylation of the gene cause carcinogenesis in colorectal cancer or not is also interesting. Another gene, 14-3-3σ, which can control cell cycle by causing G2/M arrest, is also thought to be able to affect the way of carcinogenesis. In our research we use methylation-specific poly-chain reaction (MS-PCR) to show the relationship between hypermethylation status of the promoter region of the three genes and the colorectal cancer. The results reveal that hypermethylation status of the CpG islands on the EDNRB promoter correlates with the pathologic stages of the colorectal cancer, and hypermethylation status of the CpG islands on the DLC-1 promoter correlates with the carcinoembryonic antigen (CEA) value in these patients.
參考文獻
延伸閱讀
- 徐翔（2021）。利用生物資訊學分析大腸直腸癌的關鍵基因〔碩士論文，國立臺灣師範大學〕。華藝線上圖書館。https://doi.org/10.6345/NTNU202100980
- 邱淮浩（2014）。探討吲哚化合物對大腸直腸癌細胞的腫瘤抑制機轉〔碩士論文，中山醫學大學〕。華藝線上圖書館。https://doi.org/10.6834/CSMU.2014.00046
- Wang, W. S. (2012). 基因體多型性對大腸直腸癌病患化學治療療效及毒性所產生的影響. 台灣癌症醫學雜誌, 28(1), 3-17. https://doi.org/10.6323/JoCRP.2012.28.1.1
- 鍾明宗、葉建志（2009）。抑癌基因SFRP家族在大腸直腸癌高度甲基化之研究。臺灣醫界，52(2)，76-78。https://doi.org/10.30044/TMJ.200902.0014
- 江紹瑜（2015）。Study of Tumor Suppressor Functions of Contactin 4 in Colorectal Cancer〔碩士論文，國立臺灣大學〕。華藝線上圖書館。https://doi.org/10.6342/NTU.2015.10465