Analysis of the AXIN2 Gene Expression in Non-Small Cell Lung Cancer
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Date
2005-06-??
Authors
曾若嘉
曾傑
許瀚水
王憶卿
Journal Title
Journal ISSN
Volume Title
Publisher
國立臺灣師範大學生命科學學系
Department of Life Science, NTNU
Department of Life Science, NTNU
Abstract
肺癌在世界上是最普遍的惡性腫瘤之一，並且在包括台灣的工業化國家是癌症死亡的主要原因；因此，探索哪些基因參與肺癌之形成是很重要的。Wingless (Wnt)訊號傳遞與細胞增生、活動及癌化生成是有關連的，在Wnt訊號傳遞途徑中，Axis inhibition protein 2 (AXIN2)蛋白的功能如同骨架蛋白，在β-catenin蛋白質降解過程中扮演重要角色，推測AXIN2基因在此訊號傳遞途徑中似具有腫瘤抑制功能。為瞭解在非小細胞肺癌中，AXIN2基因表現是否發生變異，我們利用反轉錄－聚合酶及免疫組織化學染色法偵測56位非小細胞肺癌及非腫瘤配對肺組織中AXIN2基因之異常。反轉錄－聚合酶分析的結果顯示，45%的病人AXIN2基因之mRNA表現有降低的情形。卡方分析發現mRNA低表現經常發生於腫瘤分期之早期病人，其比例為54% （P值為0.048），達顯著相關；另外，亦發現mRNA低表現與年老病人是有相關性的（P值為0.052）。免疫組織化學染色法分析結果顯示36%的非小細胞肺癌樣本有AXIN2蛋白質低表達之情形。卡方分析發現AXIN2蛋白質低表達經常發生於良好或中度之腫瘤分化分期（P值為0.023），達顯著相關。我們的研究結果顯示，非小細胞肺癌中AXIN2基因之mRNA及蛋白質表現的變異是經常發生的，而且可能與肺癌早期形成有關。
Lung cancer is one of the most common malignancies in the world and is the leading cause of cancer deaths in industrial countries, including Taiwan. Therefore, it is important to identify the etiologically associated gene(s) involved in lung cancer. Wingless (Wnt) signaling is involved in cellular proliferation, motility, and tumorigenesis. Axis inhibition protein 2 (AXIN2) is a scaffold protein for the degradation complex in the Wnt signaling pathway. Therefore, AXIN2 could act as a tumor suppressor. To determine whether the AXIN2 expression is altered in non-small cell lung cancer (NSCLC), we analyzed the AXIN2 mRNA and protein expression by reverse transcriptase polymerase chain reaction and immunohistochemistry in 56 NSCLC and lion-cancerous matched tissues. Our results indicated that 45% of NSCLC patients showed low mRNA expression. Chi-squared analysis indicated that low mRNA expression appeared to be more frequent in early stage (54%) than in late stage (26%) (P=0.048). A more significant correlation of low AXIN2 mRNA expression in elderly patients (57%) than in young patients (31%) (P=0.052) was observed. In addition, 36% of NSCLC patients exhibited reduction or complete loss of AXIN2 protein expression. Chi-squared analysis indicated a highly significant correlation between aberrant AXIN2 expression and differentiation, recorded as negative staining in 52% (16/31) of NSCLC with well and moderate differentiation, compared with 20% (4/20) of NSCLC with poor differentiation (P=0.023). Our data suggested that the alteration of AXIN2 expression might play an etiological role in NSCLC tumorigenesis.
Lung cancer is one of the most common malignancies in the world and is the leading cause of cancer deaths in industrial countries, including Taiwan. Therefore, it is important to identify the etiologically associated gene(s) involved in lung cancer. Wingless (Wnt) signaling is involved in cellular proliferation, motility, and tumorigenesis. Axis inhibition protein 2 (AXIN2) is a scaffold protein for the degradation complex in the Wnt signaling pathway. Therefore, AXIN2 could act as a tumor suppressor. To determine whether the AXIN2 expression is altered in non-small cell lung cancer (NSCLC), we analyzed the AXIN2 mRNA and protein expression by reverse transcriptase polymerase chain reaction and immunohistochemistry in 56 NSCLC and lion-cancerous matched tissues. Our results indicated that 45% of NSCLC patients showed low mRNA expression. Chi-squared analysis indicated that low mRNA expression appeared to be more frequent in early stage (54%) than in late stage (26%) (P=0.048). A more significant correlation of low AXIN2 mRNA expression in elderly patients (57%) than in young patients (31%) (P=0.052) was observed. In addition, 36% of NSCLC patients exhibited reduction or complete loss of AXIN2 protein expression. Chi-squared analysis indicated a highly significant correlation between aberrant AXIN2 expression and differentiation, recorded as negative staining in 52% (16/31) of NSCLC with well and moderate differentiation, compared with 20% (4/20) of NSCLC with poor differentiation (P=0.023). Our data suggested that the alteration of AXIN2 expression might play an etiological role in NSCLC tumorigenesis.