非小細胞肺癌早期診斷指標之建立

自西元1982年以來，惡性腫瘤(癌症)就高居國內民眾十大死因之首。以西元2004年為例，因惡性腫瘤死亡者佔當年國內死亡總人口數的27.20%，更是第二大死因－心臟疾病死亡率的2.8倍。而肺癌死亡率在不斷攀升下，亦已分別位居國人男、女性癌症死因之第二位和第一位。肺癌之所以有如此高的死亡率，主要是因早期診斷困難所致。當患者經過一系列檢查確認罹患肺癌時，大多已發生腫瘤轉移，造成治療效果及預後皆相當不樂觀，而且發生腫瘤轉移的肺癌患者之五年期存活率僅有5-15%。因此，建立一個能夠監測腫瘤細胞轉移之生物指標，在提高肺癌治療效果和延長肺癌患者之存活率具相當重要的意義。Cell junction(細胞接合)是負責體內組織(尤其上皮組織)之細胞與細胞、細胞與細胞外基質(ECM)之間的接合結構。其不僅具有形態學上的意義，在個體的發育過程、細胞信息的傳導、調控基因的表達、細胞運動和細胞增殖分化等生命活動中，都扮演著相當重要的角色。同時，科學家亦發現細胞接合結構的改變是許多癌變細胞，尤其是高轉移性癌細胞的重要特徵之一。最近研究發現：在肺腫瘤組織中，Cell junction中的E-cadherin及Cx43表現量可做為肺癌患者的預後指標。已知E-cadeherin 需與α-catenin、β-catenin結合形成複合體(E-cadeherin-catenin complex)鑲嵌於細胞膜上，才具有生物功能。除此，p120ctm 亦可和E-cadeherin來促進complex的功能且其表達能力與細胞複製的速度相關。本研究乃以IHC (免疫組織化學)染色法，分析與上皮細胞間之adherens junction (黏著接合)相關的E-cadherin、α-catenin、β-catenin和p120ctn等蛋白以及與gap junction(間隙接合)相關的Cx43等蛋白，在肺腫瘤組織以及與腫瘤組織周圍不同距離之非腫瘤組織中的表現。結果發現：細胞質裡與Adherens junctions相關的E-cadherin 及共同參與複合體的成員 α-catenin及β-catenin以及與gap junction相關的Cx43等蛋白表現量，均會隨著與接近腫瘤組織的距離而出現遞減的趨勢，甚至腫瘤組織大部分都無法測得這些蛋白的表現；至於p120ctn則呈現不降反昇的相反狀況。因此推測E-cadherin、α-catenin、β-catenin、p120ctn及Cx43蛋白表現或許可用來早期偵測細胞之腫瘤化程度或趨勢。

Malignant tumors have been the leading cause of death in Taiwan since 1982 and lung cancer is responsible for 15-20% of cancer deaths. Such high mortality rate of lung cancer is mainly resulted from the difficulty of early diagnosis. Most patients, when identified, have metastasis and, therefore, the treatment efficiency is relatively low, usually 5-15% of the patients with a 5-year survival. This indicates an urgent need to establish a biomarker for monitoring tumor metastasis in order to improve treatment efficiency and extend the survival of lung cancer patients. The structural changes of cell junction have been identified to be an important indicator of cancer cell, especially for those with high transfer potention. In recent studies, the expression extents of E-cadherin of cell juction in lung tumor tissues and Cx43 expression amount could be used as a prognosis indicator. E-cadherin was known to be functional only after being binding with α-catenin, β-catenin to form a complex integrated in the cell membrane. In additon, together with E-cadherin, p120ctm can promote the funtion of the complex and its ability of indication is related to the cell proliferationr rate. The paraffin section from 16 lung tumors and each of five adjacent normal tissues at various distances from tumor tissues were analyzed with the method of IHC. The results show that the protein expressions of E-cadherin and its complex, α-catenin and β-catenin, gradually decreased when their distance to tumor tissues decreased. That is, there was a positive correlation between their protein expressions and the distance to the tumor tissues. Therefore, the decrease of expression of E-cadherin, α-catenin and β-catenin could be used as a biomarker for monitoring tumorgenesis.