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Plasma IL13Rα2 as a novel liquid biopsy biomarker for glioblastoma

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Abstract

Purpose

Glioblastoma (GBM) is the most common and deadliest brain tumor with unrelenting and rapid disease progression. The standard of care for GBM is surgical excision followed by radiation with concurrent and adjuvant temozolomide-centered chemotherapy (TMZ). Treatment failure and resistance is the rule and despite advances in imaging technology, early detection of treatment failure or impending resistance remains a challenge. There is a dire, unmet, need in clinical practice for minimally-invasive diagnostic tools to enable timely understanding of disease progression and treatment response. Here, we aim to address this clinical need by leveraging a unique characteristic of GBM: the overexpression of the α2 variant of the IL-13 receptor in over 75% of GBM tumors.

Methods

In this study we examined patients with primary GBM from Penn State and Cleveland Clinic compared to healthy controls.

Results

IL13Rα2 was detectable in plasma of GBM patients using ELISA but detection could be optimized by PEG precipitation to enrich for extracellular vesicles (EVs). Patients with GBM had elevated levels of plasma IL13Rα2, which correlated to levels of this receptor in the tumor tissue. Elevated plasma levels of IL13Rα2 predicted longer overall survival (OS) (19.8 vs. 13.2 months). Similarly, detection of IL13Rα2 + cells in tumor tissue also predicted longer OS (22.1 vs. 12.2 months).

Conclusion

These findings strongly suggest that expression of the IL13Rα2 receptor confer survival advantage in GBM patients, which can be determined through a minimally-invasive liquid biopsy. Detection of plasma IL13Rα2 can also be used to select GBM patients for targeted tumor therapy.

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Acknowledgements

The authors acknowledge the Penn State Neuroscience Institute Biorepository and the Cleveland Clinic for providing tissue samples and clinical data crucial for this study. This work was partially supported by the Tara Leah Witmer Fund. The results shown here are in part based upon data generated by the TCGA Research Network: https://www.cancer.gov/tcga.

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The authors have not disclosed any funding.

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Authors and Affiliations

  1. Department of Neurosurgery, Penn State Hershey Medical Center, Hershey, PA, USA

    Vladimir Khristov, Darya Nesterova, Emily Tufano, Ganesh Shenoy, Bhavyata Pandya, Gela Beselia, Oliver Mrowczynski, Brad Zacharia & James Connor

  2. Penn State College of Medicine, Hershey, PA, USA

    Mara Trifoi, Taylor Clegg, Annika Daya, Thomas Barrett & Nataliya Smith

  3. Division of Cancer Epidemiology and Genetics, Trans-Divisional Research Program, National Cancer Institute, Shady Grove, MD, USA

    Kristin Waite & Jill Barnholtz-Sloan

  4. Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA

    Justin Lathia

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  1. Vladimir Khristov
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by VK, ET, and DN. Preparation and analysis of clinical data was performed by TC, AD, TB, KW, and NS. GS, BP, GB, OM, and BZ contributed to the study conception, design, and implementation. JL, JBS, and JC provided guidance and oversight of the project. The first draft of the manuscript was written by VK and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Vladimir Khristov.

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Khristov, V., Nesterova, D., Trifoi, M. et al. Plasma IL13Rα2 as a novel liquid biopsy biomarker for glioblastoma. J Neurooncol 160, 743–752 (2022). https://doi.org/10.1007/s11060-022-04196-0

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