The mutational landscape of circulating cell free DNA in patients with esophageal squamous cell carcinoma response and non-response to neoadjuvant chemotherapy

Author:Ruixiang Zhang, Ying Hu, Tao Zhou, Wenbo Han, Yanhui Chen, Xianben Liu, Shilei Liu, Hui Zeng,Yin Li, Henghui Zhang

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.

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.

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.

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.