Genetic testing of neoadjuvant therapy patients with esophageal cancer

Abstract

BackgroundEsophageal cancer (EC) is a prevalent malignant tumor of the upper gastrointestinal tract in China, posing a serious threat to public health. Recent advances in cancer therapy have led to the application of neoadjuvant immunotherapy for esophageal cancer. However, the gene mutations in neoadjuvant immunotherapy of esophageal cancer remain unknown. The aim of this study was to investigate the gene mutation landscape in neoadjuvant treatment of esophageal cancer, and to provide more potential biomarkers and therapeutic targets for EC. MethodsNext-generation sequencing was performed on tumor tissue and plasma samples from 18 esophageal cancer patients in this study. The mutation profiles of 425 tumor genes were compared between pathological complete response (pCR) and non-pathological complete response (no-pCR) groups after neoadjuvant immunotherapy. The tumor mutational burden (TMB) values in tissue and plasma samples were also measured and the TMB differences between the pCR and no-pCR groups at baseline tissue (T0) were analyzed. ResultsWe found that TP53, NOTCH1 and FAT1 were the top three frequently mutated genes, with frequencies of 77.8 %, 61.1 %, and 44.4 %. Notably, the frequency of FAT1 mutations was significantly higher in the pCR group than in the no-pCR group. The mutation types in T0 and P0 samples were largely concordant, except for copy number variation (CNV). Moreover, the TMB in T0 samples was significantly higher than in P0 samples. While the TMB in the pCR group was higher than in the no-pCR group at T0, but this difference was not statistically significant. ConclusionsOur results revealed a mutational profile in patients with EC after neoadjuvant immunotherapy, and found the FAT1 gene has more significant mutations in pCR patients. We found esophageal cancer with pCR showed a trend toward higher TMB. Our findings may have implications for the subsequent diagnosis or treatment of EC.