PTPRO promoter methylation is predictive of poorer outcome for HER2-positive breast cancer: indication for personalized therapy.
PTPRO promoter methylation is predictive of poorer outcome for HER2-positive breast cancer: indication for personalized therapy.
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PTPRO 启动子甲基化预示着 HER2 阳性乳腺癌的较差预后：个性化治疗的指征
DOI：
10.1186/1479-5876-11-245
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发表时间：
2013-10-03
影响因子：
7.4
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Huang YT;Li FF;Ke C;Li Z;Li ZT;Zou XF;Zheng XX;Chen YP;Zhang H
背景蛋白质酪氨酸磷酸酶受体O型（PTPRO）最近作为一种肿瘤抑制因子而受到关注，其编码基因在癌症中经常被甲基化。我们检测了乳腺癌中PTPRO基因启动子的甲基化状态，并评估了PTPRO启动子甲基化与乳腺癌患者临床病理参数和预后的相关性。方法收集221例福尔马林固定石蜡包埋（FFPE）肿瘤组织、20例FFPE正常癌旁组织和24例匹配血浆样本。 使用甲基化特异性 PCR 评估乳腺癌患者的 PTPRO 基因启动子甲基化。评估了启动子甲基化与临床病理学参数的关联。采用Kaplan-Meier生存分析和Cox比例风险模型来估计对生存的影响。结果175个样本给出了可识别的PCR产物，其中130例（74.3%）有PTPRO基因启动子甲基化。 PTPRO 甲基化与较高的组织学分级相关（P= 0.028），但与其他临床参数无关。多变量分析表明，使用甲基化 PTPRO 的 HER2 阳性患者的总生存期 (OS) 显着较差，但 ER 阳性患者的总生存期 (OS) 明显较差。甲基化-PTPRO在匹配的血浆样本中可检测到，并且仅在相应原发肿瘤也被甲基化的患者的血浆中观察到。结论PTPRO甲基化是原发性乳腺癌中的常见事件，并且可以在外周血样本中可靠地检测到。 PTPRO 甲基化仅与 HER2 阳性患者的不良生存相关，这表明使用 PTPRO 甲基化作为乳腺癌的预后因素并优化 HER2 阳性患者的个体化治疗。
BackgroundProtein Tyrosine Phosphatase Receptor-type O (PTPRO) has recently been in the spotlight as a tumor suppressor, whose encoding gene is frequently methylated in cancers. We examined the methylation status of the PTPRO gene promoter in breast cancer and evaluated the correlation between PTPRO promoter methylation and both clinicopathological parameters and prognosis of breast cancer patients.MethodsTwo hundred twenty-one formalin-fixed, paraffin-embedded (FFPE) tumor tissues, 20 FFPE normal adjacent tissues and 24 matched plasma samples, collected from primary breast cancer patients, were assessed for PTPRO gene promoter methylation using methylation-specific PCR. Associations of promoter methylation with clinicopathological parameters were evaluated. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect on survival.Results175 samples gave identifiable PCR products, of which 130 cases (74.3%) had PTPRO gene promoter methylation. PTPRO methylation correlated with higher histological grade (P= 0.028), but not other clinical parameters. Multivariate analysis indicated that overall survival (OS) was significantly poorer in HER2-positive, but not ER-positive patients with methylated-PTPRO. Methylated-PTPRO was detectable in matched plasma samples and only observed in plasma from patients whose corresponding primary tumors were also methylated.ConclusionsPTPRO methylation is a common event in the primary breast cancer and can be reliably detected in peripheral blood samples. PTPRO methylation is associated with poor survival only in HER2-positive patients, suggesting use of PTPRO methylation as a prognostic factor for breast cancer and for optimizing individualized therapy for HER2-positive patients.
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影响因子：
--
作者：
Ramezani, Fatemeh;Salami, Siamak;Maleki, Davood
通讯作者：
Maleki, Davood
影响因子：
45.3
作者：
Seidman, A;Hudis, C;Keefe, D
通讯作者：
Keefe, D
影响因子：
64.8
作者：
Curtis, Christina;Shah, Sohrab P.;Chin, Suet-Feung;Turashvili, Gulisa;Rueda, Oscar M.;Dunning, Mark J.;Speed, Doug;Lynch, Andy G.;Samarajiwa, Shamith;Yuan, Yinyin;Graef, Stefan;Ha, Gavin;Haffari, Gholamreza;Bashashati, Ali;Russell, Roslin;McKinney, Steven;Langerod, Anita;Green, Andrew;Provenzano, Elena;Wishart, Gordon;Pinder, Sarah;Watson, Peter;Markowetz, Florian;Murphy, Leigh;Ellis, Ian;Purushotham, Arnie;Borresen-Dale, Anne-Lise;Brenton, James D.;Tavare, Simon;Caldas, Carlos;Aparicio, Samuel
通讯作者：
Aparicio, Samuel
影响因子：
3.6
作者：
Swift-Scanlan, Theresa;Vang, Russell;Sukumar, Saraswati
通讯作者：
Sukumar, Saraswati
DOI：
10.1007/s00432-010-0890-z
发表时间：
2011-02-01
影响因子：
3.6
作者：
Shetty, Preetha J.;Movva, Sireesha;Hasan, Qurratulain
通讯作者：
Hasan, Qurratulain