Background: Anti-EGFR mAb are recommended treatment for metastatic colorectal cancer (mCRC). Accurate mutation profiling and disease monitoring are challenging. The current study investigates the potential use of transrenal DNA as a biomarker for disease management. Methods: Agreement between archival tissue specimens and transrenal DNA extracted from 200 post-treated mCRC patients was determined. Total DNA concentrations were measured and mutations within the KRAS and EGFR genes were profiled for each specimen. To ascertain therapy resistance; patients were serially monitored monthly. Results: Concordance measurement with matched tissues at baseline was remarkably high (92%) for EGFR and KRAS mutations. Sensitivity and specificity were 98.4% and 89.1% respectively. Newly detectable mutations for a subgroup of patients with initial wildtype characteristics were evident after 4 months of anti-EGFR mAb therapy. Survival analysis using adjusted estimates showed that patients detected by transrenal DNA for key mutations or had higher mutant DNA content had poorer outcome. Conclusion: Transrenal DNA offers new options to follow clinical treatment in mCRC. It demonstrates the ability to capture newly acquired mutations that has strong associative links to therapy resistance. Patients with these mutations fared poorly for survival outcomes and indicated possible prognostic value for transrenal DNA detection.

中文翻译：

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经肾DNA在大肠癌无创监测和预后中的潜在用途。

背景：抗EGFR mAb被推荐用于转移性结直肠癌（mCRC）的治疗。准确的突变分析和疾病监测具有挑战性。目前的研究调查了跨肾DNA作为疾病治疗生物标志物的潜在用途。方法：确定档案组织标本与从200名经过治疗的mCRC患者中提取的经肾DNA之间的一致性。测量总DNA浓度，并对每个样品分析KRAS和EGFR基因内的突变。确定治疗抵抗力；每月对患者进行连续监测。结果：在基线时与匹配组织的一致性测量对于EGFR和KRAS突变非常高（92％）。敏感性和特异性分别为98.4％和89.1％。抗EGFR mAb治疗4个月后，具有初始野生型特征的亚组患者新发现的突变很明显。使用调整后的估计值进行的生存分析显示，经经肾DNA检测到关键突变或突变DNA含量较高的患者预后较差。结论：经肾DNA为mCRC的临床治疗提供了新的选择。它证明了捕获具有与治疗抗性强相关联的新获得的突变的能力。具有这些突变的患者在生存结果方面表现不佳，并表明经肾DNA检测可能具有预后价值。使用调整后的估计值进行的生存分析显示，经经肾DNA检测到关键突变或突变DNA含量较高的患者预后较差。结论：经肾DNA为mCRC的临床治疗提供了新的选择。它证明了捕获具有与治疗抗性强相关联的新获得的突变的能力。具有这些突变的患者在生存结果方面表现不佳，并表明经肾DNA检测可能具有预后价值。使用调整后的估计值进行的生存分析显示，经经肾DNA检测到关键突变或突变DNA含量较高的患者预后较差。结论：经肾DNA为mCRC的临床治疗提供了新的选择。它证明了捕获具有与治疗抗性强相关联的新获得的突变的能力。具有这些突变的患者在生存结果方面表现不佳，并表明经肾DNA检测可能具有预后价值。