口腔麟狀上皮細胞癌中組織蛋白修飾酵素表現之臨床病理學上的研究

The clinicopathological study of histone modified enzyme expression in oral squamous cell carcinoma

楊裕閔(Yu-Min Yang)

指導教授 ： 張建國

高雄醫學大學/醫學院/醫學研究所/碩士(2009年)

https://doi.org/10.6832/KMU.2009.00087

摘要

背景：根據行政院衛生署97年度十大死因統計表，台灣地區惡性腫瘤已連續29年居冠，其中口腔癌在男性惡性腫瘤死因中已攀升至第四位。在真核細胞中，去氧核醣核酸的修飾及組織蛋白修飾是調控基因表現的兩種重要表觀基因體調控機制。去氧核醣核酸及組織蛋白甲基化、乙醯化及磷酸化與多種癌症形成有關。然而組織蛋白修飾在口腔癌細胞之表現與口腔癌的發展及預後情形是否有影響，則尚待進一步研究。
方法：本研究利用組織微矩陣及免疫組織化學染色法，偵測5種組織蛋白修飾酵素在215例口腔鱗狀細胞癌(OSCC)表現情形和OSCC病人病理參數及病人存活之關係，以探討組織蛋白修飾酵素對台灣OSCC進展及預後之可能影響。
結果：以ARK2抗體染細胞核，以存活率分析，統計上有顯著的差異(p=0.005)。以口腔癌分期，統計上具有顯著的差異(p=0.006)。依原發部位腫瘤大小分類，統計上有顯著的差異(p=0.026)。以G9a抗體染細胞質，依組織分化狀況分類，統計上具有顯著的差異(p=0.026)。以EZH2抗體染細胞核，依是否有淋巴轉移分類，統計上有顯著的差異(p=0.016)。以SUV39H1抗體染細胞核，以口腔癌分期，統計上具有顯著的差異(p=0.009)。
討論：我們的研究結果顯示，台灣口腔癌形成之早期組織蛋白甲基化H3K9、H3K27及磷酸化H3S10的表現情形可以作為OSCC患者預後的輔助指標。且OSCC病人中，ARK2大量表現者，三年存活率將會降低。

關鍵字

口腔癌 ； 組織蛋白 ； 甲基化 ； 磷酸化

並列摘要

Background: According to the Department of Health, Executive Yuan, R.O.C. (TAIWAN) , In year 2008 ”Top 10 cause of death tables “ Oral squamous cell carcinoma (OSCC) is now ranked the fourth-leading cancer deaths in Taiwanese male population. DNA methylation and histone modifications constitute the major epigenetic control mechanism of gene expression in eukaryotic cells. DNA methylation and Histone methylation, acetylation and phosphorylation are association with many types of cancer. However, histone modification in the performance, development and prognosis of oral cancer is not well understood.
Materials and Methods: We collected 215 OSCC tissues and examined expression of histone modified enzyme by using TMA and IHC. We observed the expression of histone modified enzymes (SUV39H1, SUV39H2, G9a, EZH2 and ARK2).
Results: The results of the IHC staining showed that expression of ARK2 with three-year survival in OSCC(p=0.005), expression of ARK2 with stage in OSCC (p=0.006), expression of ARK2 with T status in OSCC(p=0.026), expression of G9a with tissue grade in OSCC(p=0.026), expression of EZH2 with lymph node metastasis in OSCC(p=0.016) and expression of SUV39H1 with stage in OSCC(p=0.009) were significantly different.
Discussion: Our study results show that overexpression of Histone methylation and phosphorylation enzymes are associated with tumor proliferation and prognosis in human oral squamous cell carcinomas.

並列關鍵字

OSCC ； Histone ； Methylation ； phosphorylation

參考文獻

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