LINE-1 hypomethylation in gastric cancer, detected by bisulfite pyrosequencing, is associated with poor prognosis.
LINE-1 hypomethylation in gastric cancer, detected by bisulfite pyrosequencing, is associated with poor prognosis.
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DOI：
10.1007/s10120-012-0209-7
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发表时间：
2013-10
期刊：
影响因子：
7.4
通讯作者：
Baba, Hideo
中科院分区：
文献类型：
--
作者：
Shigaki, Hironobu;Baba, Yoshifumi;Watanabe, Masayuki;Murata, Asuka;Iwagami, Shiro;Miyake, Keisuke;Ishimoto, Takatsugu;Iwatsuki, Masaaki;Baba, Hideo
全基因组DNA低甲基化在基因组不稳定和肿瘤发生中起着重要作用。长分布的核苷酸元件-1、L1(line-1)重复元件中的DNA甲基化是全球DNA甲基化水平的良好指标。在某些类型的人类肿瘤中，LINE-1甲基化水平作为患者预后的预测标记物正引起人们的兴趣。然而，LINE-1低甲基化在胃癌中的预后意义尚不清楚。利用亚硫酸氢盐-焦磷酸测序技术，对203例胃癌切除标本中LINE-1甲基化进行了定量。采用COX比例风险模型计算危险比(HR)，并对临床和病理变量进行了调整。与匹配的正常胃粘膜相比，胃癌组织中LINE-1甲基化水平显著降低(P<0.0001)。肿瘤LINE-1甲基化范围为11.6-97.5(n=0.203；平均71.4，中位数74.4，标准差12.9)。LINE-1低甲基化与较短的总生存期显著相关[对数等级p=0.029；单变量HR 2.01，95%可信区间(CI)1.09~3.99，p=0.023；分期匹配HR 1.88，95%CI 1.02~3.74，p=0.041；多变量HR 1.98，95%CI 1.04~4.04，p=0.036]。在生存分析中，没有观察到任何协变量的显著影响修正(均为p交互作用>；0.25)。LINE-1在胃癌中的低甲基化与较短的生存期有关，这表明它有可能被用作预后生物标记物。
Genome-wide DNA hypomethylation plays an important role in genomic instability and carcinogenesis. DNA methylation in the long interspersed nucleotide element-1, L1 (LINE-1) repetitive element is a good indicator of the global DNA methylation level. In some types of human neoplasms, LINE-1 methylation level is attracting interest as a predictive marker for patient prognosis. However, the prognostic significance of LINE-1 hypomethylation in gastric cancer remains unclear. Using 203 resected gastric cancer specimens, we quantified LINE-1 methylation using bisulfite-pyrosequencing technology. A Cox proportional hazards model was used to calculate the hazard ratio (HR), adjusted for the clinical and pathological variables. Gastric cancers showed significantly lower LINE-1 methylation levels compared to matched normal gastric mucosa (p < 0.0001; n = 74). Tumoral LINE-1 methylation range was 11.6–97.5 on a 0–100 scale (n = 203; mean 71.4, median 74.4, standard deviation 12.9). LINE-1 hypomethylation was significantly associated with shorter overall survival [log-rank p = 0.029; univariate HR 2.01, 95 % confidence interval (CI) 1.09–3.99, p = 0.023; stage-matched HR 1.88, 95 % CI 1.02–3.74, p = 0.041; multivariate HR 1.98, 95 % CI 1.04–4.04, p = 0.036]. No significant effect modification was observed by any of the covariates in survival analysis (all p interaction >0.25). LINE-1 hypomethylation in gastric cancer is associated with shorter survival, suggesting that it has potential for use as a prognostic biomarker.
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影响因子：
50.3
作者：
Holm, TM;Jackson-Grusby, L;Jaenisch, R
通讯作者：
Jaenisch, R
影响因子：
56.9
作者：
Gaudet, F;Hodgson, JG;Jaenisch, R
通讯作者：
Jaenisch, R
DOI：
10.1111/j.1525-1438.2007.01117.x
发表时间：
2008-07-01
影响因子：
4.8
作者：
Pattamadilok, J.;Huapai, N.;Mutirangura, A.
通讯作者：
Mutirangura, A.
全球DNA甲基化替代线路1甲基化与MGMT启动子甲基化相关，是神经胶质瘤的更好预后因素。
影响因子：
3.7
作者：
Ohka F;Natsume A;Motomura K;Kishida Y;Kondo Y;Abe T;Nakasu Y;Namba H;Wakai K;Fukui T;Momota H;Iwami K;Kinjo S;Ito M;Fujii M;Wakabayashi T
通讯作者：
Wakabayashi T
影响因子：
7.4
作者：
Emoto, Shigenobu;Ishigami, Hironori;Kitayama, Joji
通讯作者：
Kitayama, Joji