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

doi:10.1016/j.jprot.2022.104684

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

Research output: Contribution to journal › Article › peer-review

2 Citations (Scopus)

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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 language	English
Article number	104684
Number of pages	11
Journal	Journal of Proteomics
Volume	266
Early online date	20 Jul 2022
DOIs	https://doi.org/10.1016/j.jprot.2022.104684
Publication status	Published - 30 Aug 2022

Keywords

Chemotherapy
Data-independent aquisition
MAGIC regimen
Oesophageal adenocarcinoma
Quantitative proteomics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jprot.2022.104684Licence: CC BY

Guo_2022_JoP_Identification-of-plasma_CC
Copyright © 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Final published version, 3.94 MBLicence: CC BY

ISSF Funding Mar21 - S Arya: ISSF Funding March 2021
Arya, S. (PI)
The Wellcome Trust
1/08/21 → 31/07/22
Project: Standard
Predictive value of plasma proteins: Research Studentship
Stewart, A. J. (PI)
Tenovus-Scotland
27/09/19 → 26/09/22
Project: Standard

Identification of plasma proteins associated with oesophageal cancer chemotherapeutic treatment outcomes using SWATH-MS (dataset)
Synowsky, S. A. (Creator), Shirran, S. L. (Creator) & Stewart, A. J. (Creator), PRIDE - PRoteomics IDEntifications database, 22 Aug 2022
https://www.ebi.ac.uk/pride/archive/projects/PXD032137
Dataset

Cite this

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, 266, Article 104684. https://doi.org/10.1016/j.jprot.2022.104684

@article{956ece2ffb1f4e779b03b7f27198349c,

title = "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{\textquoteright}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. ",

keywords = "Chemotherapy, Data-independent aquisition, MAGIC regimen, Oesophageal adenocarcinoma, Quantitative proteomics",

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

note = "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].",

year = "2022",

month = aug,

day = "30",

doi = "10.1016/j.jprot.2022.104684",

language = "English",

volume = "266",

journal = "Journal of Proteomics",

issn = "1874-3919",

publisher = "Elsevier",

}

Guo, N, Minas, G , Synowsky, SA, Dunne, MR, Ahmed, H, McShane, R, Bhardwaj, A, Donlon, NE, Lorton, C, O'Sullivan, J, Reynolds, JV, Caie, PD, Shirran, SL , Lynch, A , Stewart, AJ & 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

TY - JOUR

T1 - Identification of plasma proteins associated with oesophageal cancer chemotherapeutic treatment outcomes using SWATH-MS

AU - Guo, Naici

AU - Minas, Giorgos

AU - Synowsky, Silvia A.

AU - Dunne, Margaret R.

AU - Ahmed, Hasnain

AU - McShane, Rhiannon

AU - Bhardwaj, Anshul

AU - Donlon, Noel E.

AU - Lorton, Cliona

AU - O'Sullivan, Jacintha

AU - Reynolds, John V.

AU - Caie, Peter David

AU - Shirran, Sally L.

AU - Lynch, Andy

AU - Stewart, Alan J.

AU - Arya, Swati

N1 - 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].

PY - 2022/8/30

Y1 - 2022/8/30

N2 - 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.

AB - 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.

KW - Chemotherapy

KW - Data-independent aquisition

KW - MAGIC regimen

KW - Oesophageal adenocarcinoma

KW - Quantitative proteomics

U2 - 10.1016/j.jprot.2022.104684

DO - 10.1016/j.jprot.2022.104684

M3 - Article

C2 - 35842220

SN - 1874-3919

VL - 266

JO - Journal of Proteomics

JF - Journal of Proteomics

M1 - 104684

ER -

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

Abstract

Keywords

UN SDGs

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Projects

ISSF Funding Mar21 - S Arya: ISSF Funding March 2021

Predictive value of plasma proteins: Research Studentship

Datasets

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

Cite this