Discovery of novel glioma serum biomarkers by proximity extension assay

Atefeh Ghorbani; Lisa M. Avery; Dorsa Sohaei; Andrea Soosaipillai; Maxime Richer; Craig Horbinski; Katy McCortney; Wei Xu; Eleftherios P. Diamandis; Ioannis Prassas

doi:10.1186/s12014-023-09400-5

Discovery of novel glioma serum biomarkers by proximity extension assay

Atefeh Ghorbani, Lisa M. Avery, Dorsa Sohaei, Andrea Soosaipillai, Maxime Richer, Craig Horbinski, Katy McCortney, Wei Xu, Eleftherios P. Diamandis^*, Ioannis Prassas^*

^*Corresponding author for this work

Pathology

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

8 Scopus citations

Abstract

Background: Gliomas are among the most malignant tumors, with a very poor prognosis. Early diagnosis is highly desirable since it can help implement more effective treatments for smaller tumors, which have not yet extensively metastasized. Improving early diagnosis may facilitate access of patients to clinical trials and prepare them for the future availability of new disease-modifying treatments. Methods: We analyzed retrospective samples collected at diagnosis (before therapy initiation), with PEA (Olink Proteomics), quantifying about 3000 proteins. We utilized 30 plasmas from gliomas (20 glioblastomas, 5 anaplastic astrocytomas, 5 anaplastic oligodendrogliomas) and 20 meningiomas (as controls). We then analyzed the data to identify proteins which either alone, or in combination, could discriminate gliomas from meningiomas, or correlate with clinical and molecular alterations. Results: We identified 8 plasma proteins which were increased in gliomas vs. meningiomas (GFAP, NEFL, EDDM3B, PROK1, MMP3, CTRL, GP2, SPINT3) and 4 proteins which were decreased in gliomas vs. meningiomas (FABP4, ALDH3A1, IL-12B and OXT). Partition algorithms and logistic regression algorithms with two biomarkers (GFAP and FABP4) achieved sensitivity of 83% and 93% at 100% and 90% specificity, respectively. The strongest single marker was GFAP with an area under the ROC curve (AUC) of 0.86. The AUC for the GFAP-FABP4 combination was 0.98. Conclusion: PEA is a powerful new proteomic technology for biomarker discovery. GFAP and a handful of other plasma biomarkers may be useful for early glioma detection and probably, prognosis. Statement: Detecting gliomas as early as possible is highly desirable since it can significantly improve the chances of effective treatments. Reliable glioma biomarkers can timely inform glioma patients about the efficacy of their prescribed treatment. Our results reveal some novel putative glioma markers that may prove valuable, when used alone or in combination, towards improved clinical care of gliomas. In order to better appreciate the potential usefulness of these markers, their performance needs to be further validated in a larger cohort of samples.

Original language	English (US)
Article number	12
Journal	Clinical Proteomics
Volume	20
Issue number	1
DOIs	https://doi.org/10.1186/s12014-023-09400-5
State	Published - Dec 2023

Funding

This work was supported by a grant to Dr. Eleftherios P. Diamandis from the Canadian Brain Foundation, and the Canadian Cancer Society Research Institute under a SPARK Grant (Grant Number: CCS707057). The Northwestern Nervous System Tumor Bank is supported by the P50CA221747 SPORE for Translational Approaches to Brain Cancer. This work was supported by a Grant to Dr. Eleftherios P. Diamandis from the Canadian Brain Foundation, and the Canadian Cancer Society Research Institute under a SPARK Grant (Grant Number: CCS707057). The Northwestern Nervous System Tumor Bank is supported by the P50CA221747 SPORE for Translational Approaches to Brain Cancer.

Keywords

Biomarkers
Early diagnosis
Glioma
Liquid biopsy
OLINK technology
Proximity extension assay (PEA)

ASJC Scopus subject areas

Molecular Medicine
Molecular Biology
Clinical Biochemistry

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title = "Discovery of novel glioma serum biomarkers by proximity extension assay",

abstract = "Background: Gliomas are among the most malignant tumors, with a very poor prognosis. Early diagnosis is highly desirable since it can help implement more effective treatments for smaller tumors, which have not yet extensively metastasized. Improving early diagnosis may facilitate access of patients to clinical trials and prepare them for the future availability of new disease-modifying treatments. Methods: We analyzed retrospective samples collected at diagnosis (before therapy initiation), with PEA (Olink Proteomics), quantifying about 3000 proteins. We utilized 30 plasmas from gliomas (20 glioblastomas, 5 anaplastic astrocytomas, 5 anaplastic oligodendrogliomas) and 20 meningiomas (as controls). We then analyzed the data to identify proteins which either alone, or in combination, could discriminate gliomas from meningiomas, or correlate with clinical and molecular alterations. Results: We identified 8 plasma proteins which were increased in gliomas vs. meningiomas (GFAP, NEFL, EDDM3B, PROK1, MMP3, CTRL, GP2, SPINT3) and 4 proteins which were decreased in gliomas vs. meningiomas (FABP4, ALDH3A1, IL-12B and OXT). Partition algorithms and logistic regression algorithms with two biomarkers (GFAP and FABP4) achieved sensitivity of 83% and 93% at 100% and 90% specificity, respectively. The strongest single marker was GFAP with an area under the ROC curve (AUC) of 0.86. The AUC for the GFAP-FABP4 combination was 0.98. Conclusion: PEA is a powerful new proteomic technology for biomarker discovery. GFAP and a handful of other plasma biomarkers may be useful for early glioma detection and probably, prognosis. Statement: Detecting gliomas as early as possible is highly desirable since it can significantly improve the chances of effective treatments. Reliable glioma biomarkers can timely inform glioma patients about the efficacy of their prescribed treatment. Our results reveal some novel putative glioma markers that may prove valuable, when used alone or in combination, towards improved clinical care of gliomas. In order to better appreciate the potential usefulness of these markers, their performance needs to be further validated in a larger cohort of samples.",

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author = "Atefeh Ghorbani and Avery, {Lisa M.} and Dorsa Sohaei and Andrea Soosaipillai and Maxime Richer and Craig Horbinski and Katy McCortney and Wei Xu and Diamandis, {Eleftherios P.} and Ioannis Prassas",

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AU - Ghorbani, Atefeh

AU - Avery, Lisa M.

AU - Sohaei, Dorsa

AU - Soosaipillai, Andrea

AU - Richer, Maxime

AU - Horbinski, Craig

AU - McCortney, Katy

AU - Xu, Wei

AU - Diamandis, Eleftherios P.

AU - Prassas, Ioannis

PY - 2023/12

Y1 - 2023/12

N2 - Background: Gliomas are among the most malignant tumors, with a very poor prognosis. Early diagnosis is highly desirable since it can help implement more effective treatments for smaller tumors, which have not yet extensively metastasized. Improving early diagnosis may facilitate access of patients to clinical trials and prepare them for the future availability of new disease-modifying treatments. Methods: We analyzed retrospective samples collected at diagnosis (before therapy initiation), with PEA (Olink Proteomics), quantifying about 3000 proteins. We utilized 30 plasmas from gliomas (20 glioblastomas, 5 anaplastic astrocytomas, 5 anaplastic oligodendrogliomas) and 20 meningiomas (as controls). We then analyzed the data to identify proteins which either alone, or in combination, could discriminate gliomas from meningiomas, or correlate with clinical and molecular alterations. Results: We identified 8 plasma proteins which were increased in gliomas vs. meningiomas (GFAP, NEFL, EDDM3B, PROK1, MMP3, CTRL, GP2, SPINT3) and 4 proteins which were decreased in gliomas vs. meningiomas (FABP4, ALDH3A1, IL-12B and OXT). Partition algorithms and logistic regression algorithms with two biomarkers (GFAP and FABP4) achieved sensitivity of 83% and 93% at 100% and 90% specificity, respectively. The strongest single marker was GFAP with an area under the ROC curve (AUC) of 0.86. The AUC for the GFAP-FABP4 combination was 0.98. Conclusion: PEA is a powerful new proteomic technology for biomarker discovery. GFAP and a handful of other plasma biomarkers may be useful for early glioma detection and probably, prognosis. Statement: Detecting gliomas as early as possible is highly desirable since it can significantly improve the chances of effective treatments. Reliable glioma biomarkers can timely inform glioma patients about the efficacy of their prescribed treatment. Our results reveal some novel putative glioma markers that may prove valuable, when used alone or in combination, towards improved clinical care of gliomas. In order to better appreciate the potential usefulness of these markers, their performance needs to be further validated in a larger cohort of samples.

AB - Background: Gliomas are among the most malignant tumors, with a very poor prognosis. Early diagnosis is highly desirable since it can help implement more effective treatments for smaller tumors, which have not yet extensively metastasized. Improving early diagnosis may facilitate access of patients to clinical trials and prepare them for the future availability of new disease-modifying treatments. Methods: We analyzed retrospective samples collected at diagnosis (before therapy initiation), with PEA (Olink Proteomics), quantifying about 3000 proteins. We utilized 30 plasmas from gliomas (20 glioblastomas, 5 anaplastic astrocytomas, 5 anaplastic oligodendrogliomas) and 20 meningiomas (as controls). We then analyzed the data to identify proteins which either alone, or in combination, could discriminate gliomas from meningiomas, or correlate with clinical and molecular alterations. Results: We identified 8 plasma proteins which were increased in gliomas vs. meningiomas (GFAP, NEFL, EDDM3B, PROK1, MMP3, CTRL, GP2, SPINT3) and 4 proteins which were decreased in gliomas vs. meningiomas (FABP4, ALDH3A1, IL-12B and OXT). Partition algorithms and logistic regression algorithms with two biomarkers (GFAP and FABP4) achieved sensitivity of 83% and 93% at 100% and 90% specificity, respectively. The strongest single marker was GFAP with an area under the ROC curve (AUC) of 0.86. The AUC for the GFAP-FABP4 combination was 0.98. Conclusion: PEA is a powerful new proteomic technology for biomarker discovery. GFAP and a handful of other plasma biomarkers may be useful for early glioma detection and probably, prognosis. Statement: Detecting gliomas as early as possible is highly desirable since it can significantly improve the chances of effective treatments. Reliable glioma biomarkers can timely inform glioma patients about the efficacy of their prescribed treatment. Our results reveal some novel putative glioma markers that may prove valuable, when used alone or in combination, towards improved clinical care of gliomas. In order to better appreciate the potential usefulness of these markers, their performance needs to be further validated in a larger cohort of samples.

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Discovery of novel glioma serum biomarkers by proximity extension assay

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