The mutation profiles of cell-free DNA in patients with oesophageal squamous cell carcinoma who were responsive and non-responsive to neoadjuvant chemotherapy

Abstract

Background: The aim of this study was to evaluate the clinical value of plasma cell-free DNA (cfDNA) mutation profiles in patients with oesophageal squamous cell carcinoma (OSCC) who received neoadjuvant chemotherapy. Methods: Twenty-two OSCC patients received neoadjuvant chemotherapy and were divided into two groups according to their response to the therapy. Fifteen patients were in the responsive group, and seven patients were in the non-responsive group. The blood samples were collected, and the plasma cfDNA mutation profiles were sequenced by a cancer gene-targeted next-generation sequencing (NGS) panel. Results:The driver gene molecular mutation burden (MMB) was significantly higher in the non-responsive group compared with the responsive group. Furthermore, we found that the differential MMB included the DNA damage response, Wnt, PI3K, Hippo, RTK/RAS, p53, and AHR pathway. The MMB yielded an area under the receiver operation characteristic (ROC) curve of 0.89 for predicting the response to neoadjuvant chemotherapy. The cfDNA copy number variations (CNVs) yielded an area under ROC curve of 1.0 for predicting the response to neoadjuvant chemotherapy. Conclusions: The driver gene MMB and CNVs in plasma cfDNA may be potential biomarkers for predicting the response to neoadjuvant chemotherapy in patients with OSCC.

Plasma Circulating Tumor DNA Sequencing Predicts Minimal Residual Disease in Resectable Esophageal Squamous Cell Carcinoma

“…Moreover, Zhang et al explored the cfDNA mutation signature of patients with ESCC who were responsive and nonresponsive to neoadjuvant chemotherapy (NAC). It was illustrated that the driver gene molecular mutation burden (MMB) of the responsive group was significantly higher than that of the non-responsive group and that the plasma cfDNA MMB and CNVs may be used to predict the response of ESCC patients to NAC (42). Likewise, a study with a cohort of patients with early breast cancer who received NAC found that ctDNA levels after two cycles of NAC predict the local tumor response to NAC treatment, and positive baseline ctDNA is significantly associated with worse DFS and OS (43).…”

An update of Clinical value of circulating tumor DNA in esophageal cancer： a systematic review and meta- analysis

“…Nineteen studies reported on the PFS of the ctDNA [14,[27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44]. As the range of HR between these studies was 1.21 to 18.70, a significant association was observed between ctDNA-positivity in EC patients and the poorer PFS.…”

Exploiting the Molecular Basis of Oesophageal Cancer for Targeted Therapies and Biomarkers for Drug Response: Guiding Clinical Decision-Making

“…It is speculated that a tumor bearing a higher TMB level may be highly immunogenic as it is likely to harbor more neoantigens. These neoantigens can then be targeted to a higher degree by activated immune cells capable of inducing an anti-tumor immune response, which would result in a good clinical prognosis [ 37 , 41 ]. This increase in neoantigens occurs because TMB is believed to be a good indicator of the number of immunogenic neopeptides displayed on the surface of tumor cells, which influences patient response to ICIs [ 38 ].…”

“…These miRNAs profiles may also serve as lead targets for new treatments [ 20 ]. The miRNA expression profiling of OSCC is distinct from that of oesophageal adenocarcinoma [ 41 ]. Some studies analysing the expression profiles of miRNA using unsupervised hierarchical clustering demonstrated that these profiles can be used to classify different types of oesophageal cancer due to the significant differences in the miRNA profiles between these oesophageal disease groups [ 44 ].…”