周明智Ming-Chih Chou何明霖Minglin Ho醫學研究所2026-10-282004-07-062004https://handle.ncl.edu.tw/11296/cwj955https://scholars.csmu.edu.tw/handle/123456789/35052背景及目的： 抑癌基因，如：p16, DAPK, GSTP1, MGMT等，轉錄起始區CpG 位置的過度甲基化會導致基因無法被轉錄出來進而導致肺癌的產生。過去有研究指出病毒感染會使甲機轉移酶大量表現而使抑癌基因轉錄起始區發生甲基化，而本研究室過去在肺癌患者肺腫瘤組織中偵測到人類乳突瘤病毒 ( Human papillomavirus ; HPV ) 的存在。因此本研究推測這些抑癌基因的過度甲基化可能HPV感染使甲基轉移酶 1及甲基轉移酶 3b蛋白的過度表現有關。 方法： 為了了解不同腫瘤形式之肺癌患者肺腫瘤組織中甲基轉移酶 1及甲基轉移酶 3b蛋白的表現情形，本研究共收集84位原發性肺癌患者進行研究，其中包括42位肺腺癌患者及42位鱗狀上皮細胞肺癌患者，以免疫組織化學染色法進行研究。而在人類乳突瘤病毒的偵測則以巣疊式聚合酶連鎖反應進行。 結果: 甲基轉移酶1 蛋白在 84位 肺癌患者中有 29位 可偵測到，佔所有人數的 35.5%。 而甲基轉移酶3b 則有 52.4% 的人可測到 ( 44 of 84)。 本研究同時也發現當甲基轉移酶3b 蛋白過度表現時，肺癌患者有較長的存活率 (p=0.028)。此外，在人類乳突瘤病毒感染的肺組織中甲基轉移酶3b 的蛋白表現有增加的趨勢。 結論：由以上結果推測人類乳突瘤病毒感染可能是藉由誘發甲基轉移酶 3b蛋白過度表現而使基因起始區過度甲基化而抑制基因的表現進而參與肺癌的腫瘤化。Background and purpose: Environment-epigenetic interactions may play a role in the geographic variation of human cancer incidence. Aberrant hypermethylation in the CpG-rich promoter regions of many tumor suppressor genes was associated with the lack of gene transcription and thus, contributed to the formation and progression of lung cancer, such as p16, DAPK, GSTP1, MGMT, etc. Therefore, we hypothesis that the DNA methyltransferase, DNMT1 and DNMT3b will be induced in lung tumorgenesis. Methods: To directly examine DNMT1 and DNMT3b protein expression in different types of non-small cell lung tumors, 84 primary lung cancer patients including 42 adenocarcinomas and 42 squamous cell lung cancers were subjected to immunohistochemic examination. Nested-PCR were used to detect HPV infection. Results: DNMT1 immunoreactivity was observed in 29 (35.5%) of 84 lung cancer and the DNMT3b was 52.4%, 44 of 84). The incidence of decreased DNMT3b protein expression in NSCLC correlated significantly with poor tumor differentiation (p=0.028). Our data also showed that DNMT3b protein expression was associated with HPV 16/18 infection (p=0.008). Conclusion: These results suggested that the involvement of HPV infection in lung tumorigenesis of lung cancer patients in Taiwan may be mediated, at least in part, through hypermethylation to cause by induced DNMT3b protein overexpression.肺癌甲基轉移酶人類乳突瘤病毒lung cancerMethyltransferaseHPVthesis