Quantitative proteomics identifies tumour matrisome signatures in patients with non-small cell lung cancer

Helen Titmarsh; Alexander von Kriegsheim; Richard A O'Connor; Kevin Dhaliwal; Margaret C Frame; Samuel B Pattle; David Dorward; Adam Byron; Ahsan R Akram

doi:10.3389/fonc.2023.1194515

Quantitative proteomics identifies tumour matrisome signatures in patients with non-small cell lung cancer

Helen Titmarsh, Alexander von Kriegsheim, Richard A O'Connor, Kevin Dhaliwal, Margaret C Frame, Samuel B Pattle, David Dorward, Adam Byron^*, Ahsan R Akram^*

^*Corresponding author for this work

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

Abstract

Abstract
Introduction: The composition and remodelling of the extracellular matrix (ECM) are important factors in the development and progression of cancers, and the ECM is implicated in promoting tumour growth and restricting anti-tumour therapies through multiple mechanisms. The characterisation of differences in ECM composition between normal and diseased tissues may aid in identifying novel diagnostic markers, prognostic indicators and therapeutic targets for drug development.
Methods: Using tissue from non-small cell lung cancer (NSCLC) patients undergoing curative intent surgery, we characterised quantitative tumour-specific ECM proteome signatures by mass spectrometry.
Results: We identified 161 matrisome proteins differentially regulated between tumour tissue and nearby non-malignant lung tissue, and we defined a collagen hydroxylation functional protein network that is enriched in the lung tumour microenvironment. We validated two novel putative extracellular markers of NSCLC, the collagen cross-linking enzyme peroxidasin and a disintegrin and metalloproteinase with thrombospondin motifs 16 (ADAMTS16), for discrimination of malignant and non-malignant lung tissue. These proteins were up-regulated in lung tumour samples, and high PXDN and ADAMTS16 gene expression was associated with shorter survival of lung adenocarcinoma and squamous cell carcinoma patients, respectively.
Discussion: These data chart extensive remodelling of the lung extracellular niche and reveal tumour matrisome signatures in human NSCLC.

Original language	English
Journal	Frontiers in Oncology
DOIs	https://doi.org/10.3389/fonc.2023.1194515
Publication status	Published - 16 Jun 2023

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Expoiting adhesion protein networks in glioblastoma
Frame, M. (Principal Investigator), Brunton, V. (Co-investigator), Byron, A. (Co-investigator) & Pollard, S. (Co-investigator)
UK-based charities
1/05/18 → 30/04/23
Project: Research
Fibroblast activation protein expressing cancer associated fibroblasts from lung cancer as imaging biomarkers for immunotherapy stratification
Akram, A. (Principal Investigator)
UK-based charities
1/12/17 → 30/11/22
Project: Research
High resolution metabolite and peptide mass spectrometry
Von Kriegsheim, A. (Principal Investigator), Christophorou, M. (Co-investigator), Finch, A. (Co-investigator), Morton, N. (Co-investigator), Ponting, C. (Co-investigator) & Walmsley, S. (Co-investigator)
UK-based charities
2/10/17 → 1/11/22
Project: Research

Institute for Genetics and Cancer Mass Spectrometry Facility
Von Kriegsheim, A. (Manager)
Institute of Genetics and Cancer
Facility/equipment: Facility

Cite this

@article{2aa43dd5a5c5424f862bb72043865053,

title = "Quantitative proteomics identifies tumour matrisome signatures in patients with non-small cell lung cancer",

abstract = "Abstract Introduction: The composition and remodelling of the extracellular matrix (ECM) are important factors in the development and progression of cancers, and the ECM is implicated in promoting tumour growth and restricting anti-tumour therapies through multiple mechanisms. The characterisation of differences in ECM composition between normal and diseased tissues may aid in identifying novel diagnostic markers, prognostic indicators and therapeutic targets for drug development. Methods: Using tissue from non-small cell lung cancer (NSCLC) patients undergoing curative intent surgery, we characterised quantitative tumour-specific ECM proteome signatures by mass spectrometry. Results: We identified 161 matrisome proteins differentially regulated between tumour tissue and nearby non-malignant lung tissue, and we defined a collagen hydroxylation functional protein network that is enriched in the lung tumour microenvironment. We validated two novel putative extracellular markers of NSCLC, the collagen cross-linking enzyme peroxidasin and a disintegrin and metalloproteinase with thrombospondin motifs 16 (ADAMTS16), for discrimination of malignant and non-malignant lung tissue. These proteins were up-regulated in lung tumour samples, and high PXDN and ADAMTS16 gene expression was associated with shorter survival of lung adenocarcinoma and squamous cell carcinoma patients, respectively. Discussion: These data chart extensive remodelling of the lung extracellular niche and reveal tumour matrisome signatures in human NSCLC. ",

author = "Helen Titmarsh and \{von Kriegsheim\}, Alexander and O'Connor, \{Richard A\} and Kevin Dhaliwal and Frame, \{Margaret C\} and Pattle, \{Samuel B\} and David Dorward and Adam Byron and Akram, \{Ahsan R\}",

note = "Funding Information: HT was funded by the EPSRC and MRC Centre for Doctoral Training in Optical Medical Imaging (EP/L016559/1). AK was supported by a Wellcome Trust multiuser equipment grant (208402/Z/17/Z). MF was funded by Cancer Research UK (C157/A15703 and C157/A24837). AA is supported by a Cancer Research UK Clinician Scientist Fellowship (A24867). Acknowledgments Publisher Copyright: Copyright {\textcopyright} 2023 Titmarsh, von Kriegsheim, Wills, O{\textquoteright}Connor, Dhaliwal, Frame, Pattle, Dorward, Byron and Akram.",

year = "2023",

month = jun,

day = "16",

doi = "10.3389/fonc.2023.1194515",

language = "English",

journal = "Frontiers in Oncology",

issn = "2234-943X",

publisher = "Frontiers Media SA",

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T1 - Quantitative proteomics identifies tumour matrisome signatures in patients with non-small cell lung cancer

AU - Titmarsh, Helen

AU - von Kriegsheim, Alexander

AU - O'Connor, Richard A

AU - Dhaliwal, Kevin

AU - Frame, Margaret C

AU - Pattle, Samuel B

AU - Dorward, David

AU - Byron, Adam

AU - Akram, Ahsan R

N1 - Funding Information: HT was funded by the EPSRC and MRC Centre for Doctoral Training in Optical Medical Imaging (EP/L016559/1). AK was supported by a Wellcome Trust multiuser equipment grant (208402/Z/17/Z). MF was funded by Cancer Research UK (C157/A15703 and C157/A24837). AA is supported by a Cancer Research UK Clinician Scientist Fellowship (A24867). Acknowledgments Publisher Copyright: Copyright © 2023 Titmarsh, von Kriegsheim, Wills, O’Connor, Dhaliwal, Frame, Pattle, Dorward, Byron and Akram.

PY - 2023/6/16

Y1 - 2023/6/16

N2 - Abstract Introduction: The composition and remodelling of the extracellular matrix (ECM) are important factors in the development and progression of cancers, and the ECM is implicated in promoting tumour growth and restricting anti-tumour therapies through multiple mechanisms. The characterisation of differences in ECM composition between normal and diseased tissues may aid in identifying novel diagnostic markers, prognostic indicators and therapeutic targets for drug development. Methods: Using tissue from non-small cell lung cancer (NSCLC) patients undergoing curative intent surgery, we characterised quantitative tumour-specific ECM proteome signatures by mass spectrometry. Results: We identified 161 matrisome proteins differentially regulated between tumour tissue and nearby non-malignant lung tissue, and we defined a collagen hydroxylation functional protein network that is enriched in the lung tumour microenvironment. We validated two novel putative extracellular markers of NSCLC, the collagen cross-linking enzyme peroxidasin and a disintegrin and metalloproteinase with thrombospondin motifs 16 (ADAMTS16), for discrimination of malignant and non-malignant lung tissue. These proteins were up-regulated in lung tumour samples, and high PXDN and ADAMTS16 gene expression was associated with shorter survival of lung adenocarcinoma and squamous cell carcinoma patients, respectively. Discussion: These data chart extensive remodelling of the lung extracellular niche and reveal tumour matrisome signatures in human NSCLC.

AB - Abstract Introduction: The composition and remodelling of the extracellular matrix (ECM) are important factors in the development and progression of cancers, and the ECM is implicated in promoting tumour growth and restricting anti-tumour therapies through multiple mechanisms. The characterisation of differences in ECM composition between normal and diseased tissues may aid in identifying novel diagnostic markers, prognostic indicators and therapeutic targets for drug development. Methods: Using tissue from non-small cell lung cancer (NSCLC) patients undergoing curative intent surgery, we characterised quantitative tumour-specific ECM proteome signatures by mass spectrometry. Results: We identified 161 matrisome proteins differentially regulated between tumour tissue and nearby non-malignant lung tissue, and we defined a collagen hydroxylation functional protein network that is enriched in the lung tumour microenvironment. We validated two novel putative extracellular markers of NSCLC, the collagen cross-linking enzyme peroxidasin and a disintegrin and metalloproteinase with thrombospondin motifs 16 (ADAMTS16), for discrimination of malignant and non-malignant lung tissue. These proteins were up-regulated in lung tumour samples, and high PXDN and ADAMTS16 gene expression was associated with shorter survival of lung adenocarcinoma and squamous cell carcinoma patients, respectively. Discussion: These data chart extensive remodelling of the lung extracellular niche and reveal tumour matrisome signatures in human NSCLC.

U2 - 10.3389/fonc.2023.1194515

DO - 10.3389/fonc.2023.1194515

M3 - Article

SN - 2234-943X

JO - Frontiers in Oncology

JF - Frontiers in Oncology

ER -

Quantitative proteomics identifies tumour matrisome signatures in patients with non-small cell lung cancer

Abstract

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Projects

Expoiting adhesion protein networks in glioblastoma

Fibroblast activation protein expressing cancer associated fibroblasts from lung cancer as imaging biomarkers for immunotherapy stratification

High resolution metabolite and peptide mass spectrometry

Equipment

Institute for Genetics and Cancer Mass Spectrometry Facility

Cite this