探討黑色素瘤相關抗原基因家族在非小細胞肺癌之表現

Differential Expression Profile of MAGE Family in Non-Small-Cell Lung Cancer

陳彥樺(Yan-Hua Chen)

指導教授 ： 林綉茹

高雄醫學大學/醫學院/醫學研究所/碩士(2007年)

https://doi.org/10.6832/KMU.2007.00097

摘要

黑色素瘤相關抗原 (Melanoma-associated antigen, MAGE) 基因在許多不同種類的癌症當中皆會表現，但在正常組織細胞當中通常是不表現的，或是僅僅只表現在某些特定的組織當中，例如生殖細胞。也由於MAGE 基因具有此種特性，因此被視為具腫瘤特異性之抗原，也因而被應用來當作癌症免疫治療之標的。本論文之研究目的即是全面性地分析MAGE 基因家族在肺癌組織中特有之差異表現，如此不僅僅可以提供化學治療的標的基因，更可進一步當作診斷或是預後的標誌。首先我們建構一包含32 個MAGE 基因之基因陣列尼龍膜片 （membrane array） ，由此來偵測52 對非小細胞肺癌組織之MAGE 基因是否具顯著差異表現。研究結果發現，除MAGE-B1、MAGE-E2 此兩個基因沒有顯著差異表現之外，其餘MAGE 基因皆有顯著之差異表現。而肺腺癌當中MAGE-B、-C和-D這三個次家族 （subfamily） 以及MAGE-B6、-D4 這兩個次族群 （subgroup） 中皆有顯著的表現。另外，在沒有轉移的肺癌之中，MAGE-D 和-A2、-D2 這兩個次族群都有高比率的表現 （p＜0.05） 。然而在臨床的病理分期 (如原發腫瘤與淋巴結浸潤) 上面，MAGE 基因之差異性表現並未達統計上之顯著差異。但在此研究中，吾人發現許多於非小細胞肺癌中未曾被報導過具有差異性表現的MAGE 基因次族群，包含有MAGE-A5、-A7、-A8、-A9、-A11、-B3、-B4、-B10、-D2、-D3、-F1、-G1、-H1、-L2 這十四個基因次族群。本研究是首篇針對台灣地區獨特之MAGE 基因差異表現之研究。雖然目前檢體量並不足以做確切的結論，但在趨勢上可見MAGE 基因應用在診斷及預後的價值上具有無窮的潛力，且本研究應用基因陣列尼龍膜片此技術，可提供一個快速且高產量之方法來偵測整個MAGE 基因的差異性表現情形。

關鍵字

黑色素瘤相關抗原 ； 非小細胞肺癌

並列摘要

The expressions of melanoma-associated antigen (MAGE) genes vary in all sorts of tumor types, such as lung cancer, which are thought to be silent in all normal tissues except germ cells. They are by which considered as tumor-specific antigens and are ideal targets for cancer immunotherapy. A complete MAGE genes differential expression profile analysis of lung cancer can provide us not only various target genes for immunotherapy but also valuable markers for further diagnosis and prognosis. We constructed a membrane array, which was consisted 32 MAGE genes, to detect whether the differential expression profile occurred in 52 pairs of non-small cell lung cancer (NSCLC) samples. Nearly total 32 MAGE genes were differential expressed in NSCLC except MAGE-B1 and –E2. MAGE-B,-C,-D, and subgroup -B6, -D4 showed prominences in lung adenocarcinoma. High-frequency expression of MAGE-D, and subgroup-A2, -D2 were also discovered in non-metastasis group (p<0.05). However, there was no significant difference of MAGE genes differential expression shown among different primary tumor (T), nodal involvement (N) and overall stages. Several MAGE subgroup genes, such as MAGE-A5, -A7, -A8, -A9, -A11, -B3, -B4, -B10, -D2, -D3, -F1, -G1, -H1, and -L2, were first discovered to show differential expression in NSCLC. The differential expression profile of MAGE genes analysis in Taiwan was unique. Although the small size of the sample may limit the diagnostic and prognostic value of MAGE genes, the use of the membrane array can provide us a high-throughput method to detect the whole MAGE genes differential expression profile.

並列關鍵字

melanoma-associated antigen ； non-small cell lung cancer

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