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中国癌症防治杂志

中国癌症防治杂志 ›› 2019, Vol. 11 ›› Issue (2): 110-115.doi: 10.3969/j.issn.1674-5671.2019.02.05

• 肿瘤标志物专栏 • 上一篇    下一篇

基于cSMART技术检测ctDNA驱动基因突变指导非小细胞肺癌精准治疗的疗效研究

  

  1. 辽宁省肿瘤医院肿瘤内科；辽宁省乳腺癌研究重点实验室
  • 出版日期:2019-04-25 发布日期:2019-05-29
  • 通讯作者: 孙涛。 E-mail：jianong@126.com
  • 基金资助:
    辽宁省中央引导地方科技发展专项（2016-31）；辽宁省临床能力建设项目（LNCCC-C05-2015 ）

The preliminary study on ctDNA-driven gene mutation detected by cSMART and its effect on precise treatment of non-small cell lung cancer

  • Online:2019-04-25 Published:2019-05-29
  • Contact: Sun Tao. E-mail：jianong@126.com

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摘要： 目的  探讨非小细胞肺癌（non-small cell lung cancer，NSCLC）基于环化单分子扩增和重测序技术（cSMART）检测循环肿瘤DNA（ctDNA）驱动基因突变，并指导其治疗的疗效。方法 选取2016年7月至2018年12月于辽宁省肿瘤医院治疗的NSCLC患者107例，采用cSMART技术检测患者血清中EGFR，ALK，KRAS，BRAF，PIK3CA，ERBB2，ROS1，RET和MET  共9种ctDNA驱动基因的突变情况。每2~4个治疗疗程后评估9种ctDNA驱动基因突变分布，并基于NCCN指南和9种基因检测结果指导患者用药。将生存信息完整且完成后续治疗的57例NSCLC患者，按照是否遵循指导方案治疗，分为规范治疗组（n=39）和非规范治疗组（n=18），比较其疗效。 结果 基于cSMART技术检测ctDNA 9种驱动基因突变78例，无突变28例。驱动基因突变的78例患者中，单基因突变27例，双基因突变24例，3基因突变11例，4基因突变5例，5基因突变5例。106例NSCLC患者无突变26人次，累计突变160人次，其中EGFR突变61人次，ALK突变11人次（包括ALK融合和点突变），TP53和KRAS突变分别为54人次和26人次，罕见突变PIK3CA发生基因突变5人次， BRAF、MET和ERBB2发生基因突变各1人次。规范治疗组患者的中位无进展生存期较非规范治疗组患者长（10.0个月vs 5.5个月，χ2=6.420，P=0.011）。结论 基于cSMART技术测定ctDNA识别NSCLC驱动基因突变简便、无创，其中EGFR及ALK为NSCLC常见驱动突变，针对其进行靶向治疗疗效较好。

关键词: 非小细胞肺癌, 环化单分子扩增和重测序技术, 液体活检, 循环肿瘤DNA, 表皮生长因子受体, 间变淋巴瘤激酶

Abstract: Objective To investigate ctDNA-driven gene mutations in patients with non-small cell lung cancer（NSCLC） based on circulating single-molecule amplification and resequencing technology（cSMART） and guide its treatment. Methods Totals of 107 patients with NSCLC were enrolled from July 2016 to December 2018 at the Department of Oncology Medical in Liaoning Cancer Hospital. The mutations of 9 ctDNA-driven genes such as EGFR，ALK，KRAS，BRAF，PIK3CA，ERBB2，ROS1，RET and MET were detected by cSMART. After each 2-4 treatment courses，the patient's 9 ctDNA-driven genes mutation distributions were evaluated，and the patients were guided to medication based on the NCCN guidelines and 9 genes test results. A total of 57 patients with NSCLC who completed the survival information and completed the follow-up treatment were divided into the standard treatment group（n=39） and the non-standard treatment group （n=18） according to whether they followed the guidelines，and compared the therapeutic effects. Results Based on cSMART，78 cases were positive mutation and 28 cases were negative mutation. Among the 78 patients who drived gene mutations，27 patients had single gene mutation，24 patients had double gene mutations，11 patients had three gene mutations，5 patients had four gene mutations，and 5 patients had five gene mutations. 106 patients with non-small　cell lung cancer had a total of 186 mutations, including 26 without mutations and 160 mutations. Among 160 mutations，there were 61　EGFR mutations，11 ALK mutations（including ALK fusion and point mutation），54 TP53 mutations，26 KRAS mutations，5 PIK3CA mutations，1  BRAF mutation，1  MET mutation and 1 ERBB2 mutation. The median progression-free survival（mPFS） of patients receiving standard treatment was longer than that of patients receiving non-standard treatment（10.0 months vs 5.5 months χ2=6.420，P=0.011）. Conclusions It is simple and non-invasive based on cSMART assay ctDNA to identify non-small cell lung cancer drive gene mutations. EGFR and ALK are common driving mutations，and their targeted therapy are better.

Key words: Non-small cell lung cancer, cSMART, Liquid biopsy, ctDNA, EGFR, Gradient lymphoma kinase

中图分类号: 

  • R734.2