Medical Oncology Service, Catalan Institute of Oncology Badalona, Hospital Germans Trias i Pujol, Applied Research Group in Oncology (B-ARGO Group), Badalona, Spain.
Pathology Service, University Hospital Germans Trias i Pujol, Badalona, Spain.
Sci Rep. 2019 Jul 31;9(1):11125. doi: 10.1038/s41598-019-47642-2.
Circulating biomarkers in blood may provide an interesting alternative to risky tissue biopsies in the diagnosis and follow-up of glioblastoma patients. We have assessed MGMT methylation status in blood and tissue samples from unresected glioblastoma patients who had been included in the randomized GENOM-009 trial. Paired blood and tissue samples were assessed by methylation-specific PCR (MSP) and pyrosequencing (PYR). After establishing the minimum PYR cut-off that could yield a significant difference in overall survival, we assessed the sensitivity, specificity, positive predictive value and negative predictive value (NPV) of the analyses. Methylation could be detected in cfDNA by both MSP and PYR but with low concordance with results in tissue. Sensitivity was low for both methods (31% and 38%, respectively), while specificity was higher for MSP in blood than for PYR in plasma (96% vs 76%) and NPV was similar (56 vs 57%). Concordance of results in tissue by MSP and PYR was 84.3% (P < 0.001) and correlated with outcome. We conclude that detection of cfDNA in the blood of glioblastoma patients can be an alternative when tumor tissue is not available but methods for the detection of cfDNA in blood must improve before it can replace analysis in tumor tissue.
血液中的循环生物标志物可能为胶质母细胞瘤患者的诊断和随访提供一种有吸引力的风险组织活检替代方法。我们评估了未切除的胶质母细胞瘤患者的血液和组织样本中的 MGMT 甲基化状态，这些患者曾参与随机 GENOM-009 试验。通过甲基化特异性 PCR（MSP）和焦磷酸测序（PYR）评估配对的血液和组织样本。在确定可在总生存期方面产生显著差异的最小 PYR 截止值后，我们评估了分析的敏感性、特异性、阳性预测值和阴性预测值（NPV）。MSP 和 PYR 均可检测到 cfDNA 中的甲基化，但与组织结果的一致性较低。两种方法的敏感性均较低（分别为 31%和 38%），而 MSP 在血液中的特异性高于 PYR 在血浆中的特异性（96%对 76%），NPV 相似（56%对 57%）。MSP 和 PYR 在组织中的结果一致性为 84.3%（P < 0.001），与结局相关。我们得出结论，当肿瘤组织不可用时，胶质母细胞瘤患者血液中的 cfDNA 检测可以作为替代方法，但在 cfDNA 在血液中的检测方法得到改进之前，它不能替代肿瘤组织中的分析。
