摘要标题：食管鳞癌患者血浆游离DNA突变谱与新辅助化疗疗效相关性研究

Background & Aims: This study was designed to explore the plasma cell free DNA (cfDNA) mutation profile in the patients with esophageal squamous cell carcinoma (ESCC) response and non-response to neoadjuvant chemotherapy.

研究背景与目的：本研究探讨新辅助化疗应答组及无应答组的食管鳞状细胞癌患者血浆游离DNA突变谱的差异。

Methods: A total of 43 patients with ESCC were recruited for the study from the affiliated Cancer Hospital of Zhengzhou University (Henan Cancer Hospital) between April 2015 and July 2016. All subjects were received neoadjuvant chemotherapy and their blood samples were collected at baseline. The plasma cfDNA and leukocytes DNA were sequenced by cancer gene targeted NGS panel.

研究方法：纳入2015年4月至2016年7月在郑州大学附属肿瘤医院(河南省肿瘤医院)接受新辅助化疗的食管鳞癌癌患者43例，在治疗前收集患者血样本，分别提取血浆游离DNA及白细胞DNA,采用肿瘤基因捕获测序技术对血浆游离DNA及血细胞DNA样本进行测序分析。

Results: At baseline, the driver gene molecular mutation burden (MMB) of plasma cfDNA of ESCC patients in non-response group (n= 16 cases) was significantly higher than patients in response group (n=27 cases)(P<0.01). Moreover, principal component analysis showed the copy number variation (CNV) in plasma cfDNA was significantly different between ESCC patients that response and non-response to neoadjuvant chemotherapy. Compared with patients in response group, higher frequency CNV loss in GNAS, CDKN2A, UGT1A1, KIT, CDH1, and NTRK3 genes and CNV gain in PRKAR1A, KDR, BCR, ETV1, PIK3CB, ROS1, STK11, and PIK2R2 genes were detected in plasma cfDNA of patients in non-response group. CNV of plasma cfDNA had an area of 0.93 under the receiver operation characteristic curve for predicting the ESCC patient response to neoadjuvant chemotherapy.

研究结果：在新辅助化疗前，无应答组（n=16）的食管鳞癌患者血浆游离DNA的驱动基因突变负荷显著高于应答组患者（n=27）。主成分分析显示新辅助化疗应答组与无应答组食管鳞状细胞癌患者肿瘤基因拷贝数变异（CNV）有显著差异。与应答组相比，无应答组患者血浆游离DNA中检测到较高频率的GNAS,CDKN2A UGT1A1,KIT,CDH1,NTRK3基因拷贝数减少，PRKAR1A, KDR, BCR, ETV1, PIK3CB, ROS1, STK11, PIK2R2基因拷贝数扩增。采用血浆游离DNA拷贝数变异预测新辅助化疗疗效的ROC曲线下面积可达到0.93。

Conclusions: The molecular mutation burden and copy number variants of plasma cfDNA may be potential biomarkers for predicting the therapeutic response to neoadjuvant chemotherapy in esophageal squamous cell carcinoma patients.

研究结论：血浆游离DNA驱动基因突变负荷及拷贝数变异可能是预测食管鳞状细胞癌患者新辅助化疗疗效的潜在分子标志物。