Quantitative Shotgun Proteomics Unveils Candidate Novel Esophageal Adenocarcinoma (EAC)-specific Proteins

J. Robert O'neill, Hui-song Pak, Erola Pairo-castineira, Vicki Save, Simon Paterson-brown, Rudolf Nenutil, Bořivoj Vojtěšek, Ian Overton, Alex Scherl, Ted R. Hupp

Research output: Contribution to journalArticlepeer-review

Abstract

Oesophageal cancer is the eighth most common cancer worldwide and the majority of patients have systemic disease at presentation. Oesophageal 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 oesophageal and gastric samples from seven patients were subjected to LC MS/MS after tandem mass tag labelling and OFFGEL fractionation. Patient matched samples of OAC, normal oesophagus, 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 tumour -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 tumour -
specific proteins are proposed and EPCAM was demonstrated to be specifically over - expressed in primary tumours and lymph node metastases compared to surrounding normal tissues. This candidate and others proposed in this study could be developed as tumour - specific targets for novel clinical staging and therapeutic approaches
Original languageEnglish
Pages (from-to)1138-1150
Number of pages13
JournalMolecular and Cellular Proteomics
Volume16
Issue number6
Early online date23 Mar 2017
DOIs
Publication statusPublished - 23 Mar 2017

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