Preliminary study of the detection of genes related to sensitivity to concurrent chemoradiotherapy based on circulating free DNA in locally advanced esophageal squamous cell carcinoma
Wang Xiaofeng1, Liang Jun1,2
1Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; 2Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, China
Abstract：Objective To explore the genes and molecular markers related to the sensitivity to concurrent chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma. Methods The peripheral blood sample of 31 patients with locally advanced esophageal squamous cell carcinoma receiving radical concurrent chemoradiotherapy was collected and the plasma circulating free DNA (cf-DNA) was extracted before treatment. The target gene capture sequencing technology based on NovaseQ6000high-throughput sequencing platform was employed to detect the changes of target genes and tumor mutation burden (TMB). According to the short-term efficacy of chemoradiotherapy, all patients were divided into the chemoradiotherapy-sensitive group (CR+PR) and chemoradiotherapy-resistant group (SD+PD). Bioinformatics and clinical data were adopted to analyze the differences of gene mutation and TMB between two groups. Results In the sequencing data of 31 patients, the tumor-related genes with a mutation frequency above 10% were Tp53, Notch1, BRAF, FGFR4, CDKN2A, ATRX and Axin2, which were almost equally distributed between the CR+PR and SD+PD groups. High-frequency mutant genes were associated with 7 signaling pathways, mainly involved in the RTK/RAS signaling pathways. The TMB value in the CR+PR group was higher than that in the SD+PD group (P=0.04), however, the mutation rate of GXYLT1 and KRT18 genes in the SD+PD group was higher than that in the CR+PR group (P<0.05). Conclusions Tp53, Notch1 and CDKN2A may be the high-frequency mutant genes associated with the incidence and progression of esophageal squamous cell carcinoma. KRT18, GXYLT1 and TMB are closely correlated with the sensitivity to concurrent chemoradiotherapy of patients with locally advanced esophageal squamous cell carcinoma.
Wang Xiaofeng,Liang Jun. Preliminary study of the detection of genes related to sensitivity to concurrent chemoradiotherapy based on circulating free DNA in locally advanced esophageal squamous cell carcinoma[J]. Chinese Journal of Radiation Oncology, 2021, 30(9): 942-948.
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