Title

尿路上皮細胞癌之上位遺傳表現

Translated Titles

Epigenetic Expression in Urothelial Cell Carcinoma

DOI

10.6845/NCHU.2009.00872

Authors

林明鋒

Key Words

膀胱癌 ; 尿道腫瘤切除手術 ; 上位遺傳學 ; 甲基化生物晶片 ; Bladder cancer ; transurethral resection of bladder tumor (TUR-BT) ; Epigenetics ; CpG island microarray

PublicationName

中興大學生命科學系所學位論文

Volume or Term/Year and Month of Publication

2009年

Academic Degree Category

碩士

Advisor

陳全木

Content Language

繁體中文

Chinese Abstract

膀胱癌是泌尿系統第二常見的癌症,是所有泌尿系統腫瘤第二大死因,台灣地區平均每年死於泌尿道癌的患者中即有近半數是膀胱癌。在新診斷的膀胱癌病人當中,有百分之七十至八十屬於早期膀胱癌。雖然早期膀胱癌只要施以經尿道腫瘤切除手術就有不錯的治療效果,但仍有百分之三十五到七十的復發機率。依據目前的組織病理分類而言,仍無法完全預測大部分早期膀胱癌的復發及侵襲性。臨床上,偵測膀胱癌的復發可以利用膀胱鏡及尿液細胞學檢查,但是膀胱鏡屬在檢查時會非常不舒服或疼痛,且尿液細胞學檢查的敏感性不佳。依據近年來文獻的報告,某些基因與人類癌症侵襲、轉移及致病機轉可能有關。上位遺傳學,即基因上鹼基對的甲基化修飾或組蛋白修飾等,對於基因表現與否的調控機制上,扮演著一個重要角色。甲基化生物晶片是絕佳的大規模甲基化篩選平台。本研究利用此一篩選平台,針對膀胱癌細胞株與臨床膀胱癌腫瘤組織,進行基因片段之甲基化分析,發現約十七個甲基化基因在膀胱癌細胞株有明顯差異,這些差異基因以MS-PCR、COBRA、甲基化特異性核酸定序分析(bisulfite-sequencing)及免疫組織化學染色分析(IHC)的方法來進行驗證。針對TSP-1(ADAMTS19)基因的驗證,可證實TSP-1基因在尿路上皮細胞癌與膀胱癌腫瘤有高度甲基化的現象。

English Abstract

Bladder cancer is the second common cancer of genitor-urinary tract and is also the second cause of death of genitor-urinary tumor. More than half of the annual death of genitor-urinary malignancy in Taiwan is caused by bladder cancer. About 70 to 80 percent of newly diagnosed bladder cancer is early bladder cancer. Though early bladder cancer can be effectively treated by transurethral resection of bladder tumor (TUR-BT), the recurrence rate of these patients can be up to 35 to 70 percent. According to present histopathological classification, we still cannot predict the recurrent rate and progression rate of most early bladder cancer. Clinically, cystoscopy & urine cytology are standard method for follow-up. However, cystoscopy may cause pain and the sensitivity of urine cytology have made them limited ability during follow-up. Recent literatures had revealed that some genes might be related to pathogenesis, progression and metastasis of human malignant tumor. Epigenetics, including DNA methylation or histone modification of nucleotide, may play an important role in regulation of gene expression. High throughput analysis of CpG island microarray makes it to be a good tool for screening hypermethylation of genes. We used this high throughput tool to screen hypermethylated genes of urothelial cell carcinoma and found about 17 genes are hypermethylated. The methylated status of genes can be verify by MS-PCR, COBRA, bisulfite-sequencing and/or immunohistochemical stain. TSP-1(ADAMTS19) was verified to be hypermethylated .

Topic Category 生命科學院 > 生命科學系所
生物農學 > 生物科學
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