Department of Integrative Oncology, Affiliated Cancer Hospital of Shantou University Medical College, Shantou 515041, China.
J Transl Med. 2013 Oct 3;11:245. doi: 10.1186/1479-5876-11-245.
Protein 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.
Two 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.
175 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.
PTPRO 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.
蛋白酪氨酸磷酸酯酶受体 O（PTPRO）作为一种肿瘤抑制因子，其编码基因在癌症中经常发生甲基化，最近成为研究热点。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。
我们使用甲基化特异性 PCR 检测了 221 例福尔马林固定、石蜡包埋（FFPE）的肿瘤组织、20 例 FFPE 正常相邻组织和 24 例配对的血浆样本中 PTPRO 基因启动子的甲基化状态。评估了启动子甲基化与临床病理参数的相关性。采用 Kaplan-Meier 生存分析和 Cox 比例风险模型估计对生存的影响。
175 个样本可获得可识别的 PCR 产物，其中 130 例（74.3%）存在 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。多因素分析表明，在 HER2 阳性而非 ER 阳性患者中，PTPRO 甲基化与总生存（OS）显著相关。在匹配的血浆样本中可检测到甲基化的 PTPRO，并且仅在其相应的原发性肿瘤也发生甲基化的患者的血浆中观察到。
PTPRO 甲基化是原发性乳腺癌的常见事件，可在周围血样中可靠检测。PTPRO 甲基化仅与 HER2 阳性患者的生存不良相关，提示 PTPRO 甲基化可作为乳腺癌的预后因素，并可优化 HER2 阳性患者的个体化治疗。
