RASSF1A promoter hypermethylation is a strong biomarker of poor survival in patients with salivary adenoid cystic carcinoma in a Chinese population.
RASSF1A promoter hypermethylation is a strong biomarker of poor survival in patients with salivary adenoid cystic carcinoma in a Chinese population.
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RASSF1A 启动子高甲基化是中国人群唾液腺腺样囊性癌患者生存不良的一个强有力的生物标志物
DOI：
10.1371/journal.pone.0110159
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Zhang CY;Zhao YX;Xia RH;Han J;Wang BS;Tian Z;Wang LZ;Hu YH;Li J
除了临床病理学参数外，分子生物标志物在癌症患者的预后评估中变得越来越重要。本研究旨在确定RAS相关结构域家族蛋白1A基因（RASSF 1A）在涎腺腺样囊性癌（ACC）中的分子改变，并评估这种改变作为预后标志物的潜力。采用亚硫酸氢盐测序PCR（BSP）和/或甲基化特异性PCR（MSP）对167例ACC肿瘤组织和50例匹配的正常涎腺组织样本进行RASSF 1A启动子甲基化状态分析。通过检测位于3 p21的两个微卫星标记（D3 S1478、D3 S1621）分析50例ACC肿瘤组织和匹配的正常涎腺组织的杂合性丢失（洛）。采用直接测序法检测50例肿瘤和正常组织中RASSF 1A基因6个外显子的突变。总的来说，RASSF 1A基因启动子甲基化在35.3%（59/167）的ACC组织中检测到，并与组织学实体瘤类型（P = 0.002）和晚期TNM分期（P = 0.014）相关。 RASSF 1A基因洛丢失率为18.0%（9/50），未发现RASSF 1A基因体细胞突变。RASSF 1A基因启动子甲基化与总生存率（Log-rank检验，P <0.001）和无病生存率（Log-rank检验，P <0.001）相关，并被鉴定为总患者生存率（P = 0.009）和无病生存率（P <0.001）的独立预测因子。 结论：RASSF 1A甲基化参与ACC的发生、分化和进展，是中国人群ACC患者生存不良的一个强有力的独立生物标志物。
In addition to the clinicopathological parameters, molecular biomarkers are becoming increasingly important in the prognostic evaluation of cancer patients. This study aimed to determine the molecular alterations in the RAS association domain family protein1A gene (RASSF1A) in salivary adenoid cystic carcinoma (ACC) and to evaluate the potential of such alterations as prognostic markers. One hundred and sixty-seven ACC tumor tissues and 50 samples of matched normal salivary gland tissues from the same patients were analyzed for RASSF1A promoter methylation status by bisulfite sequencing PCR (BSP) and/or methylation-specific PCR (MSP). Fifty ACC tumor tissues and matched normal salivary gland tissues were analyzed for loss of heterozygosity (LOH) by examining two microsatellite markers (D3S1478, D3S1621) at 3p21. RASSF1A gene mutations were detected by direct sequencing of all six exons in 50 tumor and normal tissue specimens. Over-all, RASSF1A promoter hypermethylation was detected in 35.3% (59/167) of ACC tissues and was associated with histologically solid tumor pattern (P = 0.002) and advanced TNM stage (P = 0.014). RASSF1A LOH was observed in 18.0% (9/50) of cases, and no somatic mutation of RASSF1A was detected in any cases. RASSF1A promoter methylation was associated with the poor over-all survival (Log-rank test, P <0.001) and disease-free survival (Log-rank test, P <0.001) and identified as an independent predicator of over-all patient survival (P = 0.009) and disease-free survival (P <0.001). It was concluded that RASSF1A methylation is involved in the development, differentiation and progression of ACC and is a strong independent biomarker of poor survival in ACC patients in a Chinese population.
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影响因子：
30.8
作者：
Dammann, R;Li, C;Pfeifer, GP
通讯作者：
Pfeifer, GP
影响因子：
8
作者：
Oliveira, C;Velho, R;Schwartz, S
通讯作者：
Schwartz, S
DOI：
10.1007/978-1-61779-316-5_3
发表时间：
2011-01-01
期刊：
EPIGENETICS PROTOCOLS, SECOND EDITION
影响因子：
--
作者：
Ku, Ja-Lok;Jeon, You-Kyung;Park, Jae-Gahb
通讯作者：
Park, Jae-Gahb
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：
11.5
作者：
de Fraipont, Florence;Levallet, Guenaelle;Zalcman, Gerard
通讯作者：
Zalcman, Gerard