Aquaporin-1 promoter hypermethylation is associated with improved prognosis in salivary gland adenoid cystic carcinoma.
Aquaporin-1 promoter hypermethylation is associated with improved prognosis in salivary gland adenoid cystic carcinoma.
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DOI：
10.1177/0194599814521569
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发表时间：
2014-05
期刊：
影响因子：
--
通讯作者：
Ha PK
中科院分区：
文献类型：
--
作者：
Tan M;Shao C;Bishop JA;Feng Z;Trock BJ;Westra WH;Ha PK
水通道蛋白-1（AQP1）是腺样囊性癌（ACC）中表观遗传修饰的候选癌基因。我们试图（1）评估ACC队列中AQP1启动子甲基化和表达，（2）确定AQP1与临床结局之间的相关性，（3）探索AQP1在体外肿瘤进展中的作用。实验室研究，回顾性病历审查。学术医疗中心。从ACC肿瘤和对照唾液腺组织中分离DNA和RNA。对亚硫酸氢盐处理的DNA进行定量甲基化特异性聚合酶链反应（PCR）。cDNA合成后进行定量逆转录PCR。产生稳定过表达AQP1质粒或空载体的细胞系。进行细胞划痕和基质胶侵袭测定。进行回顾性病历审查以收集临床信息。来自77个肿瘤和30个对照的甲基化结果表明，AQP1在肿瘤中是低甲基化的（P <0.0001）。与对照组相比，58例肿瘤（75.3%）显示AQP1低甲基化。在58例肿瘤和23例对照中评估的AQP1表达水平显示出肿瘤表达增加的趋势（P =.08）。单因素分析显示AQP1高甲基化与总生存率增加相关。AQP1表达水平与细胞存活率无相关性，AQP1过表达不影响细胞体外迁移和侵袭能力。AQP1启动子低甲基化在ACC中很常见，并且AQP1在这些肿瘤中倾向于过表达。单变量分析显示，AQP1甲基化增加与预后改善相关，但表达与预后无关。需要进一步的体外研究来阐明AQP1在ACC中的作用。
Aquaporin-1 (AQP1) is a candidate oncogene that is epigenetically modified in adenoid cystic carcinoma (ACC). We sought to (1) assess AQP1 promoter methylation and expression in an ACC cohort, (2) identify correlations between AQP1 and clinical outcomes, and (3) explore the role of AQP1 in tumor progression in vitro. Laboratory study, retrospective chart review. Academic medical center. DNA and RNA were isolated from ACC tumors and control salivary gland tissues. Quantitative methylation-specific polymerase chain reaction (PCR) was performed on bisulfite-treated DNA. Quantitative reverse transcription PCR was performed after cDNA synthesis. Cell lines stably overexpressing an AQP1 plasmid or empty vector were generated. Cell scratch and Matrigel invasion assays were performed. Retrospective chart review was performed for collection of clinical information. Methylation results from 77 tumors and 30 controls demonstrated that AQP1 was hypomethylated in tumors (P < .0001). Fifty-eight tumors (75.3%) displayed AQP1 hypomethylation compared with controls. AQP1 expression levels assessed in 58 tumors and 23 controls demonstrated a trend toward increased expression in tumors (P = .08). Univariate analysis revealed that AQP1 hypermethylation was associated with increased overall survival. No associations between AQP1 expression level and survival were found. AQP1 overexpression did not affect cell migratory or invasive capacities in vitro. AQP1 promoter hypomethylation is common in ACC, and AQP1 tends to be overexpressed in these tumors. Increased AQP1 methylation is associated with improved prognosis on univariate analysis, but expression is not associated with outcomes. Further in vitro studies are necessary to clarify the role of AQP1 in ACC.
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DOI：
10.1158/1078-0432.ccr-10-2992
发表时间：
2011-07-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Shao C;Sun W;Tan M;Glazer CA;Bhan S;Zhong X;Fakhry C;Sharma R;Westra WH;Hoque MO;Moskaluk CA;Sidransky D;Califano JA;Ha PK
通讯作者：
Ha PK
影响因子：
3.3
作者：
Machida, Yuichiro;Ueda, Yoshimichi;Sakuma, Tsutomu
通讯作者：
Sakuma, Tsutomu
影响因子：
6.2
作者：
Li, J;El-Naggar, A;Mao, L
通讯作者：
Mao, L
影响因子：
4.8
作者：
Shao, Chunbo;Bai, Weiliang;Ha, Patrick K.
通讯作者：
Ha, Patrick K.
DOI：
10.1002/hed.21849
发表时间：
2012-11
影响因子：
2.9
作者：
Liu, Jia;Shao, Chunbo;Tan, Marietta L.;Mu, David;Ferris, Robert L.;Ha, Patrick K.
通讯作者：
Ha, Patrick K.