自1982年起，癌症即為台灣地區十大死亡原因之第一位，其中肺癌不論在女性或男性都高居癌症死亡率的首位，儘管目前醫學已相當進步，但對於分子致癌機制仍未完全釐清。目前所知，癌症形成的原因，是由於多重基因發生變異所造成，其中大家所熟知和癌症有關的為抑癌基因 (tumor suppressor gene) 及致癌基因 (oncogene)。因此，抑癌基因變異的研究有助於了解癌症形成的機制。 研究目的：Growth arrest-specific 7 (GAS7) 這個蛋白質為GAS這個基因家族的其中一個成員，主要功能可能與調控細胞週期有關；前人研究報導顯示，GAS7可能在細胞中扮演一抑癌基因的角色。因此，本研究目的在探討GAS7基因在台灣地區非小細胞肺癌 (non-small cell lung cancer) 病人細胞中之變異情形：利用免疫組織化學染色法，觀察病人組織切片中GAS7蛋白表現情形，再以反轉錄—聚合酵素鏈反應分析組織細胞中mRNA轉錄是否異常，續以甲基化為基礎的定序反應以及微衛星基因座鑑定法分別偵測GAS7基因的促進子過度甲基化頻率和基因座缺失頻率。 結果: 本研究以免疫組織化學染色法發現75位NSCLC病人中GAS7蛋白低表達頻率為57.3% (43/75)，以31位病人之組織進行西方轉漬法發現三種主要的蛋白形式，分別依分子量大至小為GAS7C、7B和7A，其GAS7C蛋白低表現之比例為48.4% (15/31)，GAS7B蛋白低表現之比例為40.7% (11/27)，而GAS7A蛋白幾乎不表現；GAS7 mRNA isoform: GAS7C和GAS7B低表達頻率分別為20.9% (19/91)和32.6% (30/92)，而GAS7C和7B啟動子甲基化頻率分別為16.7% (6/36) 和65.6% (21/32)。GAS7基因座缺失的頻率在位於基因上、下游兩微衛星序列取聯集後為20.7% (18/87)。GAS7蛋白質/mRNA、GAS7C和7B之mRNA/啟動子甲基化的數據彼此間都呈現統計上的顯著相關性 (P<0.05)。利用西方轉漬膠片中相對於GAS7C分子量之蛋白進行膠體內水解、trypsin反應及質譜分析，本研究證實其為GAS7C蛋白。同時，我們藉由不同肺細胞株一系列的基因及蛋白質實驗，我們發現GAS7蛋白不同isoforms如GAS7C和7B，表達的量與細胞內的位置也都不同。 結論：本研究證實GAS7基因在台灣地區肺癌形成過程中扮演一個類似抑癌基因的角色，其中GAS7C為主要的變異蛋白，其變異主要機制為啟動子過度甲基化及基因座缺失，而 GAS7C 蛋白則可以在生長較為緩慢之正常肺細胞表現，此研究也是首篇證實GAS7C isoform可以在人類細胞中表現之論文。

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