Identification of novel molecular subgroups in esophageal adenocarcinoma to predict response to neo-adjuvant therapies

Esophageal adenocarcinoma (EAC) is a highly aggressive cancer and its response to chemo-, and radiotherapy is unpredictable. EAC are highly heterogeneous at the molecular level. The aim of this study was to perform gene expression analysis of EAC to identify distinct molecular subgroups and to investigate expression signatures in relation to treatment response. In this prospective observational study, RNA sequencing was performed on pre-treatment endoscopic EAC biopsies from a discovery cohort included between 2012 and 2017 in one Dutch Academic Center. Four additional cohorts were analyzed for validation purposes. Unsupervised clustering was performed on 107 patients to identify biological EAC subgroups. Specific cell signaling profiles were identified and evaluated with respect to predicting response to neoadjuvant chemo(radio)therapy.