Identification of plasma proteins associated with oesophageal cancer chemotherapeutic treatment outcomes using SWATH-MS
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.
Citation
Guo , N , Minas , G , Synowsky , S A , Dunne , M R , Ahmed , H , McShane , R , Bhardwaj , A , Donlon , N E , Lorton , C , O'Sullivan , J , Reynolds , J V , Caie , P D , Shirran , S L , Lynch , A , Stewart , A J & Arya , S 2022 , ' Identification of plasma proteins associated with oesophageal cancer chemotherapeutic treatment outcomes using SWATH-MS ' , Journal of Proteomics , vol. 266 , 104684 . https://doi.org/10.1016/j.jprot.2022.104684
Publication
Journal of Proteomics
Status
Peer reviewed
ISSN
1874-3919Type
Journal article
Description
Authors wish to thank the Wellcome Trust for funding the purchase of the TripleTOF 5600+ mass spectrometer [grant number: 094476/Z/10/Z] and their Institutional Strategic Support Fund [grant number: 097831/Z/11/Z] for funding a transition fellowship (to S.A.). We also wish to thank Tenovus Scotland for PhD studentship funding [grant number: T19-05]; to R.M and H.A. M.R.D. is funded by the Health Research Board, Ireland [grant number: HRB-ILP-POR-2017-055].Collections
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