Proteomic analysis to identify markers for response to neoadjuvant treatment in esophageal and gastroesophageal cancer

Abstract

Background Esophageal cancer represents a global challenge. Despite significant evolution of treatment protocols in the past decade, recurrence rates are still high and survival rates are poor. Current treatment paradigm for localized gastroesophageal junction (GEJ) carcinoma remains to be further elucidated as for the role of neoadjuvant chemoradiation versus perioperative chemotherapy. Aim To identify biomarkers for response to chemoradiation in esophageal and gastroesophageal cancer, we performed an in‐depth proteomic analysis of esophageal and gastroesophageal tumors, to describe differences in pathway activation between patients with favorable and poor prognosis following neoadjuvant chemoradiation. Methods Patients with locally advanced esophageal and gastroesophageal cancer following neoadjuvant chemoradiation were included in the cohort. The study cohort was dichotomized into two groups of patients, named “favorable prognosis” and “poor prognosis” according to the postoperative disease‐free interval. We performed a mass spectrometry analysis of proteins extracted from the malignant regions of surgical specimens and analyzed data from electronic medical records. Clinical data was correlated with differences in protein expression between patient with a favorable and poor prognosis using validated gene expression pathways. Results The study included 35 patients with adenocarcinoma. All patients in this cohort had esophageal adenocarcinoma. Patients median age was 62 years. Twenty‐five (71.3%) patients underwent neoadjuvant chemoradiation, and 28.7% underwent neoadjuvant chemotherapy only. A proteomic analysis of our cohort identified 2885 proteins. Enrichment levels of 98 of these proteins differed significantly between favorable and poor prognosis cohorts in patients who underwent neoadjuvant chemoradiation ( p < .05) but not in patients who underwent neoadjuvant chemotherapy. The favorable prognosis patients group analysis exhibited differential enrichment of 87 proteins related to cellular respiration and oxidative phosphorylation pathways as well as proteins of the RAS oncogene family. Conclusion In this study we identified differential enrichment of pathways related to oxidative phosphorylation and RAS oncogene pathway in esophageal cancer patients with a favorable response to chemoradiation. Following further validation, our findings may portray potential surrogate signature of biomarkers based upon these pathways.

Naa10p promotes cell invasiveness of esophageal cancer by coordinating the c-Myc and PAI1 regulatory axis

“…Esophageal cancer (ESCA) is an aggressive malignancy with poor therapeutic outcomes [ 1 ]. Alterations in proteins and posttranslational modifications (PTMs) leading to the pathogenesis of ESCA have attracted much research attention [ 2 , 3 ]. Since large-scale genome profiling has identified several driver mutations and key regulation pathways but effective targeted therapy is still lacking, discovering novel pathological alterations in proteins may give rise to advances in drug development to fulfill the gap in current drug targets.…”