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Biomark Res. 2017 Nov 10;5:32. doi: 10.1186/s40364-017-0112-9. eCollection 2017.

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

Lim SY1,2, Lee JH1,2, Welsh SJ1,2, Ahn SB1, Breen E3, Khan A3, Carlino MS2,4,5, Menzies AM2,4,6, Kefford RF1,2,5, Scolyer RA2,4, Long GV2,4,6, Rizos H1,2,7.

Author information

1
Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia.
2
Melanoma Institute Australia, Sydney, Australia.
3
Australian Proteome Analysis Facility, Macquarie University, Sydney, Australia.
4
Sydney Medical School, University of Sydney, Sydney, Australia.
5
Westmead Hospital, Sydney, Australia.
6
Royal North Shore and Mater Hospitals, Sydney, Australia.
7
Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, 2 Technology Place, Macquarie University, Sydney, NSW 2109 Australia.

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 aptamer-based 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.

KEYWORDS:

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

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