Therawis Diagnostics GmbH, Grillparzerstrasse 14, 81675, Munich, Germany.
Institute of Pathology, Klinikum rechts der Isar, Technische Universität München, Ismaninger Strasse 22, 81675, Munich, Germany.
Sci Rep. 2018 Nov 15;8(1):16861. doi: 10.1038/s41598-018-34919-1.
Significant evidence has accumulated that DNA-methylation of the paired-like homeodomain transcription factor 2 (PITX2) gene can serve as a prognostic and predictive biomarker in breast cancer. PITX2 DNA-methylation data have been obtained so far from microarray and polymerase chain reaction (PCR)-based research tests. The availability of an analytically validated in vitro methylation-specific real-time PCR assay format (therascreen PITX2 RGQ PCR assay) intended for the determination of the percent methylation ratio (PMR) in the (PITX2) promoter 2 prompted us to investigate whether the clinical performance of these different assay systems generate comparable clinical outcome data. Mathematically converted microarray data of a previous breast cancer study (n = 204) into PMR values leads to a PITX2 cut-off value at PMR 14.73. Recalculation of the data to experimentally equivalent PMRs with the PCR PITX2 assay leads to a cut-off value at PMR 12 with the highest statistical significance. This cut-off predicts outcome of high-risk breast cancer patients to adjuvant anthracycline-based chemotherapy (n = 204; Hazard Ratio 2.48; p < 0.001) comparable to microarray generated results (n = 204; Hazard ratio 2.32; p < 0.0001). The therascreen PITX2 RGQ PCR assay is an analytically validated test with high reliability and robustness and predicts outcome of high-risk breast cancer patients to anthracycline-based chemotherapy.
大量证据表明，配对样同源结构域转录因子 2（PITX2）基因的 DNA 甲基化可用作乳腺癌的预后和预测生物标志物。迄今为止，已经从微阵列和聚合酶链反应（PCR）为基础的研究测试中获得了 PITX2 DNA 甲基化数据。用于确定（PITX2）启动子 2 中甲基化比例（PMR）的分析验证的体外甲基化特异性实时 PCR 测定法（therascreen PITX2 RGQ PCR 测定法）的可用性促使我们研究这些不同测定系统的临床性能是否产生可比的临床结果数据。将先前乳腺癌研究（n=204）的微阵列数据转换为 PMR 值，会得到一个 PMR 值为 14.73 的 PITX2 截止值。用 PCR PITX2 测定法将数据重新计算为实验等效的 PMR 值，会得到一个 PMR 值为 12 的截止值，其具有最高的统计学意义。该截止值可预测接受辅助蒽环类药物化疗的高危乳腺癌患者的结局（n=204；危险比 2.48；p<0.001），与微阵列生成的结果（n=204；危险比 2.32；p<0.0001）相当。therascreen PITX2 RGQ PCR 测定法是一种经过分析验证的测试，具有高度可靠性和稳健性，可预测接受蒽环类药物化疗的高危乳腺癌患者的结局。
