結腸直腸癌基因差別表現之研究

Abstract

大腸直腸癌是許多西方國家中常見的疾病之一，在許多國家中均高居十 大癌症死因的第一位。在台灣，隨著社會的日漸富裕，生活型態的改變， 大腸直腸癌病例有逐年升增加之趨勢，目前已居十大癌症死因的第三位。 一般認為大腸直腸癌的發生與飲食、遺傳均有關係，只要能早期發現，予 以治療，大腸直腸癌的存活率極高，但至目前為止，並無一有效而簡便的 方法能對大腸直腸癌作早期偵測及預後診斷。因此，瞭解大腸直腸癌的致 癌機轉，並找尋特定的生化標記成為目前極其迫切的工作。本實驗利用近 年專門針對比較基因表現差異所開發出的差異表現法，進行大腸直腸癌正 常組織與腫瘤組織間基因表現差異之研究。在篩選過10,000條基因之mRNA ，並經北方墨點法驗證後，挑選出四條具表現差異之基因的cDNA片段。將 此四條cDNA片段經選殖定序與北方墨點法再確認後，得到一在腫瘤組織中 表現量升高之6028A-1基因cDNA片段。以此基因進行臨床檢體篩選的結果 ，發現該基因於Dukes* B3期後的腫瘤組織中，表現量顯著的升高，而且 此表現量差異的現象可觀察到具有性別關連性，即在男性的腫瘤組織中， 該基因表現量升高的程度較女性為明顯。而此基因表現量差異的情形，相 對於腫瘤發生部位，則觀察不到相關性。由於尚未得到此基因之全部序列 圖譜，因此有關此段基因之進一步資訊，仍有待後續實驗加以研究。 Colorectal adenocarcinoma occurs in approximately 2500 persons per year and is the third leading cause of the cancer mortality in Taiwan. If diagnosed at its early staging, the 5-year survival rates will be higher than 50%. However, the lack of an effective early-detection screening method is the major barrier to improve the treatment of patients with colorectal cancer. For reasons of this, searching for biomarkers specific to colorectal cancer has become an important issue now, since such markers will usefIn this study, a recently developed mRNA differential display technique is employed to screen tumor marker genes of colorectal cancer. The mRNA differential display technique has the potential to identify those genes with altered expression in different cells. By using this method, more than 10,000 mRNA species were screened. One of them, 6028A-1, showed significant change in gene expression and had been confirm by Northern blot analysis. The cDNA fragment of this gene had been cloned and sequenced. But theAfter clinical screening of multi-patients blotting, this gene showed an elevation of gene expression in tumor tissue as cancer progressing from Dukes* B2 to Dukes* B3. This phenomenon is more remarkable in the specimens of male than female. By analyzing with other parameters, the gene expression showed no alteration with respect to the tumor site.rential display technique is employed to screen tumor marker genes of colorectal cancer. The mRNA differential display technique has the potential to identify those genes with altered expression in different cells. By using this method, more than 10,000 mRNA species were screened. One of them, 6028A-1, showed significant change in gene expression and had been confirm by Northern blot analysis. The cDNA fragment of this gene had been cloned and sequenced. But theAfter clinical screening of multi-patients blotting, this gene showed an elevation of gene expression in tumor tissue as cancer progressing from Dukes* B2 to Dukes* B3. This phenomenon is more remarkable in the specimens of male than female. By analyzing with other parameters, the gene expression showed no alteration with respect to the tumor site.loped mRNA differential display technique is employed to screen tumor marker genes of colorectal cancer. The mRNA differential display technique has the potential to identify those genes with altered expression in different cells. By using this method, more than 10,000 mRNA species were screened. One of them, 6028A-1, showed significant change in gene