Salta Sofia, P Nunes Sandra, Fontes-Sousa Mário, Lopes Paula, Freitas Micaela, Caldas Margarida, Antunes Luís, Castro Fernando, Antunes Pedro, Palma de Sousa Susana, Henrique Rui, Jerónimo Carmen
Cancer Biology & Epigenetics Group-Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), 4200-072 Porto, Portugal.
Master in Oncology, Institute of Biomedical Sciences Abel Salazar-University of Porto (ICBAS-UP), 4050-313 Porto, Portugal.
J Clin Med. 2018 Nov 7;7(11):420. doi: 10.3390/jcm7110420.
Breast cancer (BrC) is the most frequent neoplasm in women. New biomarkers, including aberrant DNA methylation, may improve BrC management. Herein, we evaluated the detection and prognostic performance of seven genes' promoter methylation (, , , , , and ).
Methylation levels were assessed in primary BrC tissues by quantitative methylation-specific polymerase chain reaction (QMSP) and in circulating cell-free DNA (ccfDNA) by multiplex QMSP from two independent cohorts of patients (Cohort #1, = 137; and Cohort #2, = 44). Receiver operating characteristic (ROC) curves were constructed, and log-rank test and Cox regression were performed to assess the prognostic value of genes' methylation levels.
The gene-panel , , , discriminated normal from cancerous tissue with high accuracy (95.55%). In multivariable analysis, high -methylation levels [>percentile 75 (P75)] associated with longer disease-free survival, whereas higher -methylation levels (>P75) associated with shorter disease-specific survival. The best performing panel in ccfDNA (, and ) disclosed a sensitivity, specificity and accuracy over 70%.
This approach enables BrC accurate diagnosis and prognostic stratification in tissue samples, and allows for early detection in liquid biopsies, thus suggesting a putative value for patient management.
乳腺癌是女性中最常见的肿瘤。包括异常DNA甲基化在内的新生物标志物可能会改善乳腺癌的管理。在此，我们评估了7个基因（、、、、、和）启动子甲基化的检测及预后性能。
通过定量甲基化特异性聚合酶链反应（QMSP）评估原发性乳腺癌组织中的甲基化水平，并通过多重QMSP评估两个独立患者队列（队列#1，=137；队列#2，=44）循环游离DNA（ccfDNA）中的甲基化水平。构建受试者工作特征（ROC）曲线，并进行对数秩检验和Cox回归以评估基因甲基化水平的预后价值。
基因组合、、、能够高精度地区分正常组织与癌组织（95.55%）。在多变量分析中，高甲基化水平[>第75百分位数（P75）]与更长的无病生存期相关，而高甲基化水平（>P75）与更短的疾病特异性生存期相关。ccfDNA中表现最佳的组合（、和）的敏感性、特异性和准确性超过70%。
这种方法能够在组织样本中实现乳腺癌的准确诊断和预后分层，并能在液体活检中实现早期检测，因此对患者管理具有潜在价值。
