LINE-1甲基化程度與第三期大腸直腸癌症接受根除手術病患合併FOLFOX化療後之術後復發有關

LINE-1 Methylation Correlates to Postoperative Recurrence in Stage III CRC Patients Following Radical Resection and FOLFOX Chemotherapy

羅云婷(Yun-Ting Lou)

指導教授 ： 王照元

高雄醫學大學/醫學院/醫學遺傳學研究所/碩士(2013年)

摘要

背景: LINE-1 甲基化程度一般被認為可用來代表全基因組甲基化狀
態，其在維持基因組穩定及表現中發揮了關鍵重要的作用。我們希望
進行研究評估LINE-1 甲基化狀態和第三期大腸直腸癌患者術後預後
之間的關聯。
材料與方法: 於2008 年1 月至2012 年7 月之間，共有129 第三期大
腸直腸癌接受根治性切除手術與後續FOLFOX 化療治療之患者參與
本研究。主要監測結果包括術後復發和癌症特異性死亡率。
結果: 129 例腫瘤之LINE-1 甲基化程度其範圍介於37.4 至77.9% （平均值為63.3，中位數為63.7，標準差7.1）。單變數分析中，LINE-1低甲基化狀態常見於年紀大於65 歲患者及術後復發病患中（兩者檢驗之p 值皆<0.05）。多變數分析中， 我們發現LINE-1 甲基化較低之族群(甲基化閾值為70.15％），與甲基化較高患者進行術後復發比較存活分析時, 具有較差的預後與較短的無疾病存活時間(Log rank test,p=0.01), 同時經過校正後也具有較高的術後復發風險（校正OR=14.107，95％CI = 1.776-112.089）。
結論: 第三期大腸直腸癌接受根治性切除手術和FOLFOX 化療治療
之患者其LINE-1 低甲基化程度與術後復發及較差的無疾病存活期之
風險顯著增加

關鍵字

LINE-1甲基化 ； 大腸直腸癌

並列摘要

Background: Methylation levels of long interspersed nucleotide elements (LINE-1) are representative of genome-wide methylation status and play a crucial role in maintaining genomic stability and gene expression. We aim to evaluate the association between LINE-1 methylation status and postoperative oncological outcome in stage III
colorectal cancer (CRC) patients.
Materials and Methods: Between Jan 2008 and July 2012, 129 stage III CRC patients following radical resection and FOLFOX chemotherapy were enrolled for the present study. Outcome measurement included postoperative recurrence and cancer-specific mortality.
Results: LINE-1 methylation level of 129 cases ranged from 37.4 to 77.9% (mean 63.3; median 63.7, standard deviation 7.1). In the univariate analysis, LINE-1 hypomethylation was more common in those who aged above and of 65 years and the patients with postoperative recurrence (both p<0.05). In the multivariate analysis, with introducing a cutoff
value of 70.15%, Kaplan-Meier analysis depicted the low methylation group had more recurrences with shorter disease free survival (Log rank test, p=0.01), and those with lower LINE-1 methylation level had a higher adjusted risk of postoperative recurrence (adjusted OR = 14.107, 95% CI
=1.776-112.089).
Conclusion: Stage III CRC patients following radical resection and FOLFOX chemotherapy with LINE-1 hypomethylation status showed a significantly increased risk of postoperative recurrence and poorer disease-free survival

並列關鍵字

LINE-1 Methylation ； colorectal cancer

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