Abstract
Esophageal cancer is the eighth most common cancer worldwide and the majority of patients have systemic disease at presentation. Esophageal adenocarcinoma (OAC), the predominant subtype in western countries, is largely resistant to current chemotherapy regimens. Selective markers are needed to enhance clinical staging and to allow targeted therapies yet there are minimal proteomic data on this cancer type. After histological review, lysates from OAC and matched normal esophageal and gastric samples from seven patients were subjected to LC MS/MS after tandem mass tag labeling and OFFGEL fractionation. Patient matched samples of OAC, normal esophagus, normal stomach, lymph node metastases and uninvolved lymph nodes were used from an additional 115 patients for verification of expression by immunohistochemistry (IHC).Over six thousand proteins were identified and quantified across samples. Quantitative reproducibility was excellent between technical replicates and a moderate correlation was seen across samples with the same histology. The quantitative accuracy was verified across the dynamic range for seven proteins by immunohistochemistry (IHC) on the originating tissues. Multiple novel tumor-specific candidates are proposed and EPCAM was verified by IHC.This shotgun proteomic study of OAC used a comparative quantitative approach to reveal proteins highly expressed in specific tissue types. Novel tumor-specific proteins are proposed and EPCAM was demonstrated to be specifically overexpressed in primary tumors and lymph node metastases compared with surrounding normal tissues. This candidate and others proposed in this study could be developed as tumor-specific targets for novel clinical staging and therapeutic approaches.
Highlights
Esophageal cancer is the eighth most common cancer worldwide and the majority of patients have systemic disease at presentation
Novel tumor-specific proteins are proposed and EPCAM was demonstrated to be overexpressed in primary tumors and lymph node metastases compared with surrounding normal tissues
To determine the specificity of EPCAM for esophageal adenocarcinoma (EAC) cells compared with surrounding normal tissues, protein expression was determined by IHC using a tissue microarray consisting; normal gastric tissue, normal squamous tissue, uninvolved lymph nodes, involved lymph nodes and primary tumor samples from resection specimens from 115 patients whom had undergone surgical resection for EAC (Fig. 5)
Summary
Female 52 ACC Eso Lower 2xCF ILE 83 mm Ͼ1 mm 3.0 mm R0 Poor N N N ypT2 ypN1 1 23 IIB IV Yes 47.6 months (censored) 47.6 months (censored). The esophagus was not included in this profiling effort gastrointestinal tissues with columnar epithelia showed similar expression patterns [16] This comparative approach has been employed in a large proteomic study of 30 human tissues by label-free quantification and again tissue-specific expression patterns identified [17]. This biomarker discovery study used a quantitative shotgun proteomic strategy to evaluate protein expression in EAC and adjacent matched normal squamous and gastric tissues from seven patients. The accuracy of this approach was confirmed by immunohistochemistry for multiple candidates and a potential tumor biomarker verified in a cohort of 115 patients with resected EAC and matched normal and metastatic tissues
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