Evaluation of two high-throughput proteomic technologies for plasma biomarker discovery in immunotherapy-treated melanoma patients.

Su Yin Lim, Jenny Lee, Sarah J. Welsh, Seong Beom Ahn, Edmond Breen, Alamgir Khan, Matteo S. Carlino, Alexander M. Menzies, Richard F. Kefford, Richard A. Scolyer, Georgina V. Long, Helen Rizos

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background: Selective kinase and immune checkpoint inhibitors, and their combinations, have significantly improved the survival of patients with advanced metastatic melanoma. Not all patients will respond to treatment however, and some patients will present with significant toxicities. Hence, the identification of biomarkers is critical for the selection and management of patients receiving treatment. Biomarker discovery often involves proteomic techniques that simultaneously profile multiple proteins but few studies have compared these platforms.

Methods: In this study, we used the multiplex bead-based Eve Technologies Discovery assay and the aptamerbased SomaLogic SOMAscan assay to identify circulating proteins predictive of response to immunotherapy in melanoma patients treated with combination immune checkpoint inhibitors. Expression of four plasma proteins were further validated using the bead-based Millipore Milliplex assay.

Results: Both the Discovery and the SOMAscan assays detected circulating plasma proteins in immunotherapy-treated melanoma patients. However, these widely used assays showed limited correlation in relative protein quantification, due to differences in specificity and the dynamic range of protein detection. Protein data derived from the Discovery and Milliplex bead-based assays were highly correlated.

Conclusions: Our study highlights significant limitations imposed by inconsistent sensitivity and specificity due to differences in the detection antibodies or aptamers of these widespread biomarker discovery approaches. Our findings emphasize the need to improve these technologies for the accurate identification of biomarkers.
LanguageEnglish
Article number32
Pages1-12
Number of pages12
JournalBiomarker research
Volume5
DOIs
Publication statusPublished - 2017

Fingerprint

Biomarkers
Proteomics
Immunotherapy
Melanoma
Assays
Throughput
Technology
Plasmas
Proteins
Blood Proteins
Patient Selection
Phosphotransferases
Toxicity
Sensitivity and Specificity
Survival
Antibodies
Therapeutics

Bibliographical note

Copyright the Author(s) 2017. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • Cytokines
  • Multiplexing
  • Luminex
  • Aptamers
  • SOMAscan
  • Biomarkers
  • Liquid biopsies
  • Immune checkpoint inhibitors
  • Melanoma

Cite this

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title = "Evaluation of two high-throughput proteomic technologies for plasma biomarker discovery in immunotherapy-treated melanoma patients.",
abstract = "Background: Selective kinase and immune checkpoint inhibitors, and their combinations, have significantly improved the survival of patients with advanced metastatic melanoma. Not all patients will respond to treatment however, and some patients will present with significant toxicities. Hence, the identification of biomarkers is critical for the selection and management of patients receiving treatment. Biomarker discovery often involves proteomic techniques that simultaneously profile multiple proteins but few studies have compared these platforms.Methods: In this study, we used the multiplex bead-based Eve Technologies Discovery assay and the aptamerbased SomaLogic SOMAscan assay to identify circulating proteins predictive of response to immunotherapy in melanoma patients treated with combination immune checkpoint inhibitors. Expression of four plasma proteins were further validated using the bead-based Millipore Milliplex assay.Results: Both the Discovery and the SOMAscan assays detected circulating plasma proteins in immunotherapy-treated melanoma patients. However, these widely used assays showed limited correlation in relative protein quantification, due to differences in specificity and the dynamic range of protein detection. Protein data derived from the Discovery and Milliplex bead-based assays were highly correlated. Conclusions: Our study highlights significant limitations imposed by inconsistent sensitivity and specificity due to differences in the detection antibodies or aptamers of these widespread biomarker discovery approaches. Our findings emphasize the need to improve these technologies for the accurate identification of biomarkers.",
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author = "Lim, {Su Yin} and Jenny Lee and Welsh, {Sarah J.} and Ahn, {Seong Beom} and Edmond Breen and Alamgir Khan and Carlino, {Matteo S.} and Menzies, {Alexander M.} and Kefford, {Richard F.} and Scolyer, {Richard A.} and Long, {Georgina V.} and Helen Rizos",
note = "Copyright the Author(s) 2017. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.",
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language = "English",
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Evaluation of two high-throughput proteomic technologies for plasma biomarker discovery in immunotherapy-treated melanoma patients. / Lim, Su Yin; Lee, Jenny; Welsh, Sarah J.; Ahn, Seong Beom; Breen, Edmond; Khan, Alamgir; Carlino, Matteo S.; Menzies, Alexander M.; Kefford, Richard F.; Scolyer, Richard A.; Long, Georgina V.; Rizos, Helen.

In: Biomarker research, Vol. 5, 32, 2017, p. 1-12.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Evaluation of two high-throughput proteomic technologies for plasma biomarker discovery in immunotherapy-treated melanoma patients.

AU - Lim, Su Yin

AU - Lee, Jenny

AU - Welsh, Sarah J.

AU - Ahn, Seong Beom

AU - Breen, Edmond

AU - Khan, Alamgir

AU - Carlino, Matteo S.

AU - Menzies, Alexander M.

AU - Kefford, Richard F.

AU - Scolyer, Richard A.

AU - Long, Georgina V.

AU - Rizos, Helen

N1 - Copyright the Author(s) 2017. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2017

Y1 - 2017

N2 - Background: Selective kinase and immune checkpoint inhibitors, and their combinations, have significantly improved the survival of patients with advanced metastatic melanoma. Not all patients will respond to treatment however, and some patients will present with significant toxicities. Hence, the identification of biomarkers is critical for the selection and management of patients receiving treatment. Biomarker discovery often involves proteomic techniques that simultaneously profile multiple proteins but few studies have compared these platforms.Methods: In this study, we used the multiplex bead-based Eve Technologies Discovery assay and the aptamerbased SomaLogic SOMAscan assay to identify circulating proteins predictive of response to immunotherapy in melanoma patients treated with combination immune checkpoint inhibitors. Expression of four plasma proteins were further validated using the bead-based Millipore Milliplex assay.Results: Both the Discovery and the SOMAscan assays detected circulating plasma proteins in immunotherapy-treated melanoma patients. However, these widely used assays showed limited correlation in relative protein quantification, due to differences in specificity and the dynamic range of protein detection. Protein data derived from the Discovery and Milliplex bead-based assays were highly correlated. Conclusions: Our study highlights significant limitations imposed by inconsistent sensitivity and specificity due to differences in the detection antibodies or aptamers of these widespread biomarker discovery approaches. Our findings emphasize the need to improve these technologies for the accurate identification of biomarkers.

AB - Background: Selective kinase and immune checkpoint inhibitors, and their combinations, have significantly improved the survival of patients with advanced metastatic melanoma. Not all patients will respond to treatment however, and some patients will present with significant toxicities. Hence, the identification of biomarkers is critical for the selection and management of patients receiving treatment. Biomarker discovery often involves proteomic techniques that simultaneously profile multiple proteins but few studies have compared these platforms.Methods: In this study, we used the multiplex bead-based Eve Technologies Discovery assay and the aptamerbased SomaLogic SOMAscan assay to identify circulating proteins predictive of response to immunotherapy in melanoma patients treated with combination immune checkpoint inhibitors. Expression of four plasma proteins were further validated using the bead-based Millipore Milliplex assay.Results: Both the Discovery and the SOMAscan assays detected circulating plasma proteins in immunotherapy-treated melanoma patients. However, these widely used assays showed limited correlation in relative protein quantification, due to differences in specificity and the dynamic range of protein detection. Protein data derived from the Discovery and Milliplex bead-based assays were highly correlated. Conclusions: Our study highlights significant limitations imposed by inconsistent sensitivity and specificity due to differences in the detection antibodies or aptamers of these widespread biomarker discovery approaches. Our findings emphasize the need to improve these technologies for the accurate identification of biomarkers.

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KW - Multiplexing

KW - Luminex

KW - Aptamers

KW - SOMAscan

KW - Biomarkers

KW - Liquid biopsies

KW - Immune checkpoint inhibitors

KW - Melanoma

U2 - 10.1186/s40364-017-0112-9

DO - 10.1186/s40364-017-0112-9

M3 - Article

VL - 5

SP - 1

EP - 12

JO - Biomarker research

T2 - Biomarker research

JF - Biomarker research

SN - 2050-7771

M1 - 32

ER -