Validation of new, circulating biomarkers for gliomas

Miyo K. Chatanaka; Lisa M. Avery; Eleftherios P. Diamandis

doi:10.1515/dx-2025-0012

Article

Validation of new, circulating biomarkers for gliomas

Miyo K. Chatanaka , Lisa M. Avery and Eleftherios P. Diamandis

Published/Copyright: March 26, 2025

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From the journal Diagnosis Volume 12 Issue 3

Abstract

Objectives

Biomarkers are useful clinical tools but only a handful of them are used routinely for patient care. Despite intense efforts to discover new, clinically useful biomarkers, very few new circulating biomarkers were implemented in clinical practice in the last 40 years. This is mainly due to rather poor clinical performance. Here, our goal was to validate the performance of a group of newly discovered circulating biomarkers for glioma by comparing our data with data from a paper recently published in Science Advances.

Methods

We analyzed our own sets of clinical samples (gliomas (n=30), meningiomas (n=20)) and a different analytical assay (Proximity Extension Assay, OLINK Proteomics) to compare the results of Shen and colleagues.

Results

Despite the sophistication of the utilized discovery method by the original investigators, we found that the newly proposed biomarkers for glioma (the best one presumably being SERPINA6) did not perform as originally claimed.

Conclusions

Scientific irreproducibility has been extensively discussed in the literature. A large proportion of newly discovered candidate biomarkers likely represent “false discovery” and significantly contribute to the propagation of irreproducible results between investigators. One of the best ways to assess the value of any new biomarker is by independent and extensive validation. Based on our previous classification of irreproducible results, we believe that this new work likely represents another example of biomarker false discovery.

Keywords: biomarkers; glioma; false discovery; biomarker failures; SERPINA6; biomarker validation

Corresponding author: Dr. Eleftherios P. Diamandis, MD, PhD, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Room L6-201, 60 Murray St., Toronto, ON, M5T 3L9, Canada, E-mail: diamandis@lunenfeld.ca

Research ethics: We previously obtained ethics certificates from the Research Ethics Board at Mount Sinai Hospital, Toronto, Canada (REB #21-0114-E), which has been renewed until August 4, 2025. Samples were provided by the Northwester University Brain Tumor Biobank.
Informed consent: Not applicable.
Author contributions: MKC drafted and edited the manuscript, and prepared Figure 2. LMA performed the statistical analysis, prepared Figures 1 and 2 and edited the manuscript. EPD conceptualized, drafted and edited the manuscript.
Use of Large Language Models, AI and Machine Learning Tools: Not applicable.
Conflict of interest: The authors state no conflict of interest.
Research funding: Our previous work was supported by a grant to EPD 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. The current work did not use any funding.
Data availability: To be shared upon request.

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Received: 2025-01-23

Accepted: 2025-02-28

Published Online: 2025-03-26

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Articles in the same Issue

https://doi.org/10.1515/dx-2025-0012

Keywords for this article

biomarkers; glioma; false discovery; biomarker failures; SERPINA6; biomarker validation