Identification of plasma proteins associated with oesophageal cancer chemotherapeutic treatment outcomes using SWATH-MS

Naici Guo, Giorgos Minas, Silvia A. Synowsky, Margaret R. Dunne, Hasnain Ahmed, Rhiannon McShane, Anshul Bhardwaj, Noel E. Donlon, Cliona Lorton, Jacintha O'Sullivan, John V. Reynolds, Peter David Caie, Sally L. Shirran, Andy Lynch, Alan J. Stewart*, Swati Arya*

*Corresponding author for this work

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Abstract

Oesophageal adenocarcinoma (OAC) is an aggressive cancer with a five-year survival of <15%. Current chemotherapeutic strategies only benefit a minority (20-30%) of patients and there are no methods available to differentiate between responders and non-responders. We performed quantitative proteomics using Sequential Window Acquisition of all THeoretical fragment-ion spectra-Mass Spectrometry (SWATH-MS) on albumin/IgG-depleted and non-depleted plasma samples from 23 patients with locally advanced OAC prior to treatment. Individuals were grouped based on tumour regression (TRG) score (TRG1/2/3 vs TRG4/5) after chemotherapy, and differentially abundant proteins were compared. Protein depletion of highly abundant proteins led to the identification of around twice as many proteins. SWATH-MS revealed significant quantitative differences in the abundance of several proteins between the two groups. These included complement c1q subunit proteins, C1QA, C1QB and C1QC, which were of higher abundance in the low TRG group. Of those that were found to be of higher abundance in the high TRG group, glutathione S-transferase pi (GSTP1) exhibited the lowest p-value and highest classification accuracy and Cohen’s kappa value. Concentrations of these proteins were further examined using ELISA-based assays. This study provides quantitative information relating to differences in the plasma proteome that underpin response to chemotherapeutic treatment in oesophageal cancers.
Original languageEnglish
Article number104684
Number of pages11
JournalJournal of Proteomics
Volume266
Early online date20 Jul 2022
DOIs
Publication statusPublished - 30 Aug 2022

Keywords

  • Chemotherapy
  • Data-independent aquisition
  • MAGIC regimen
  • Oesophageal adenocarcinoma
  • Quantitative proteomics

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