演題

PN4-7

胆嚢癌におけるCDO1遺伝子プロモーター領域のDNAメチル化の臨床的意義

[演者] 五十嵐 一晴:1
[著者] 山下 継史:1, 西澤 伸恭:1, 西山 亮:1, 河又 寛:1, 田島 弘:1, 海津 貴史:1, 隈元 雄介:1, 渡邊 昌彦:1
1:北里大学病院 外科

Background
Using a pharmacological unmasking microarray, we previously identified promotor DNA methylation of the cysteine dioxygenase 1 (CDO1) gene in various human cancers. In this study, we assessed the clinicopathological significance of CDO1 methylation in primary gallbladder cancer (GBC) for the first time.
Methods
CDO1 DNA methylation was quantified using quantitative TaqMan methylation specific PCR (Q-MSP) in 99 primary GBC patients who underwent surgical resection between 1986 and 2014.
Results
The median CDO1 TaqMeth value of primary GBCs was 16.5, and the values ranged from 0 to 106. These values were significantly higher than those of corresponding non-tumor tissue (median 1.9; ranging from 0 to 72, p=0.0014). Using a cut-off value of 17.7, which was optimally calculated using log-rank plot analysis, GBC cases with CDO1 hypermethylation (n=47) showed significantly poorer prognosis than those with CDO1 hypomethylation (n=52) (p=0.0023). CDO1 hypermethylation was significantly associated with pT factor (p=0.006), vascular permeation (p=0.0082), and pStage (p=0.017). Multivariate Cox proportional hazards analysis identified that CDO1 hypermethylation, as well as high lymphatic permeation and resection status, were independent prognostic factors. Notably, CDO1 hypermethylation showed prognostic relevance, especially in stage II GBC, in which it is highly anticipated to function as a predictive marker for candidates of adjuvant therapy.
Conclusions
Promotor DNA methylation of CDO1 was demonstrated for the first time to be a cancer-associated methylation in primary GBC, and it has the potential to be a prognostic biomarker of GBC independent of stage for high-risk patients with stage II GBC.
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