Verification of a Blood-Based Targeted Proteomics Signature for Malignant Pleural Mesothelioma.
Journal
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
ISSN: 1538-7755
Titre abrégé: Cancer Epidemiol Biomarkers Prev
Pays: United States
ID NLM: 9200608
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
10
04
2020
revised:
18
06
2020
accepted:
27
07
2020
pubmed:
1
8
2020
medline:
22
12
2021
entrez:
1
8
2020
Statut:
ppublish
Résumé
We have verified a mass spectrometry (MS)-based targeted proteomics signature for the detection of malignant pleural mesothelioma (MPM) from the blood. A seven-peptide biomarker MPM signature by targeted proteomics in serum was identified in a previous independent study. Here, we have verified the predictive accuracy of a reduced version of that signature, now composed of six-peptide biomarkers. We have applied liquid chromatography-selected reaction monitoring (LC-SRM), also known as multiple-reaction monitoring (MRM), for the investigation of 402 serum samples from 213 patients with MPM and 189 cancer-free asbestos-exposed donors from the United States, Australia, and Europe. Each of the biomarkers composing the signature was independently informative, with no apparent functional or physical relation to each other. The multiplexing possibility offered by MS proteomics allowed their integration into a single signature with a higher discriminating capacity than that of the single biomarkers alone. The strategy allowed in this way to increase their potential utility for clinical decisions. The signature discriminated patients with MPM and asbestos-exposed donors with AUC of 0.738. For early-stage MPM, AUC was 0.765. This signature was also prognostic, and Kaplan-Meier analysis showed a significant difference between high- and low-risk groups with an HR of 1.659 (95% CI, 1.075-2.562; Targeted proteomics allowed the development of a multianalyte signature with diagnostic and prognostic potential for MPM from the blood. The proteomic signature represents an additional diagnostic approach for informing clinical decisions for patients at risk for MPM.
Sections du résumé
BACKGROUND
We have verified a mass spectrometry (MS)-based targeted proteomics signature for the detection of malignant pleural mesothelioma (MPM) from the blood.
METHODS
A seven-peptide biomarker MPM signature by targeted proteomics in serum was identified in a previous independent study. Here, we have verified the predictive accuracy of a reduced version of that signature, now composed of six-peptide biomarkers. We have applied liquid chromatography-selected reaction monitoring (LC-SRM), also known as multiple-reaction monitoring (MRM), for the investigation of 402 serum samples from 213 patients with MPM and 189 cancer-free asbestos-exposed donors from the United States, Australia, and Europe.
RESULTS
Each of the biomarkers composing the signature was independently informative, with no apparent functional or physical relation to each other. The multiplexing possibility offered by MS proteomics allowed their integration into a single signature with a higher discriminating capacity than that of the single biomarkers alone. The strategy allowed in this way to increase their potential utility for clinical decisions. The signature discriminated patients with MPM and asbestos-exposed donors with AUC of 0.738. For early-stage MPM, AUC was 0.765. This signature was also prognostic, and Kaplan-Meier analysis showed a significant difference between high- and low-risk groups with an HR of 1.659 (95% CI, 1.075-2.562;
CONCLUSIONS
Targeted proteomics allowed the development of a multianalyte signature with diagnostic and prognostic potential for MPM from the blood.
IMPACT
The proteomic signature represents an additional diagnostic approach for informing clinical decisions for patients at risk for MPM.
Identifiants
pubmed: 32732250
pii: 1055-9965.EPI-20-0543
doi: 10.1158/1055-9965.EPI-20-0543
pmc: PMC7541795
mid: NIHMS1617211
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1973-1982Subventions
Organisme : NCI NIH HHS
ID : U01 CA111295
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA214195
Pays : United States
Informations de copyright
©2020 American Association for Cancer Research.
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