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尿液循环肿瘤 DNA 检测在非小细胞肺癌不同分期患者 EGFR 突变中的应用。

Utility of urinary circulating tumor DNA for EGFR mutation detection in different stages of non-small cell lung cancer patients.

机构信息

Department of Respiratory Medicine, Wuhan No. 6 Hospital, Affiliated Hospital to Jianghan University, 168 Xianggang Rd, Wuhan, 430072, People's Republic of China.

出版信息

Clin Transl Oncol. 2017 Oct;19(10):1283-1291. doi: 10.1007/s12094-017-1669-3. Epub 2017 May 11.

DOI:10.1007/s12094-017-1669-3
PMID:28497422
Abstract

PURPOSE

Non-invasive methods of molecular profiling for non-small cell lung cancer (NSCLC) are useful for monitoring disease progression. The aim of the current study was to ascertain if transrenal DNA is sensitive for clinical correlation and EGFR detection in NSCLC patients.

METHODS

160 patients at various stages of the disease participated and samples were collected prospectively at 2-month intervals. A baseline sample was taken before treatment commencement. To ascertain the sensitivity of transrenal DNA, we compared its results with plasma DNA. ddPCR was used to profile the urine and blood samples for key EGFR mutations.

RESULTS

Using tumor tissues as references, our study showed good concordance in EGFR mutations with transrenal DNA before treatment. Results were highly matching in late-stage NSCLC patients, with stage III/IV patients yielding an agreement of more than 90%. The assay was also sensitive to detect early-stage patients after surgical procedures. Profiles were highly concordant with results derived from plasma DNA, demonstrating the specificity of transrenal DNA assays. Serial monitoring of these patients showed stable molecular signatures and correlated to different treatments. Survival analysis showed good prognostic utility for late-stage patients with high transrenal DNA variations and patients that acquired T790M mutation.

CONCLUSION

The study demonstrated the feasibility of using transrenal DNA in mutation profiling for different stages of NSCLC patients. It highlights the importance of continual monitoring and has potential clinical utility in the clinical management of NSCLC.

摘要

目的

非小细胞肺癌(NSCLC)的非侵入性分子分析方法有助于监测疾病进展。本研究旨在确定跨肾 DNA 是否能敏感地用于 NSCLC 患者的临床相关性和 EGFR 检测。

方法

160 名处于不同疾病阶段的患者参与了本研究,并在每 2 个月的时间间隔内进行了前瞻性样本采集。在开始治疗前采集基线样本。为了确定跨肾 DNA 的敏感性,我们将其结果与血浆 DNA 进行了比较。ddPCR 用于分析尿液和血液样本中的关键 EGFR 突变。

结果

使用肿瘤组织作为参考,我们的研究表明,治疗前跨肾 DNA 与 EGFR 突变具有良好的一致性。晚期 NSCLC 患者的结果高度匹配,III/IV 期患者的一致性超过 90%。该检测还能够检测手术治疗后的早期患者。与从血浆 DNA 获得的结果高度一致,证明了跨肾 DNA 检测的特异性。对这些患者的连续监测显示出稳定的分子特征,并与不同的治疗方法相关。生存分析显示,晚期患者的高跨肾 DNA 变异和获得 T790M 突变的患者具有良好的预后预测能力。

结论

该研究证明了在不同阶段的 NSCLC 患者中使用跨肾 DNA 进行突变分析的可行性。它强调了持续监测的重要性,并在 NSCLC 的临床管理中具有潜在的临床应用价值。

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