Cell Reports Medicine (Oct 2020)
Tumor-Educated Platelet RNA for the Detection and (Pseudo)progression Monitoring of Glioblastoma
- Nik Sol,
- Sjors G.J.G. in ‘t Veld,
- Adrienne Vancura,
- Maud Tjerkstra,
- Cyra Leurs,
- François Rustenburg,
- Pepijn Schellen,
- Heleen Verschueren,
- Edward Post,
- Kenn Zwaan,
- Jip Ramaker,
- Laurine E. Wedekind,
- Jihane Tannous,
- Bauke Ylstra,
- Joep Killestein,
- Farrah Mateen,
- Sander Idema,
- Philip C. de Witt Hamer,
- Anna C. Navis,
- William P.J. Leenders,
- Ann Hoeben,
- Bastiaan Moraal,
- David P. Noske,
- W. Peter Vandertop,
- R. Jonas A. Nilsson,
- Bakhos A. Tannous,
- Pieter Wesseling,
- Jaap C. Reijneveld,
- Myron G. Best,
- Thomas Wurdinger
Affiliations
- Nik Sol
- Brain Tumor Center Amsterdam, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands; Department of Neurology, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands; Corresponding author
- Sjors G.J.G. in ‘t Veld
- Brain Tumor Center Amsterdam, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands; Department of Neurosurgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands
- Adrienne Vancura
- Brain Tumor Center Amsterdam, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands; Department of Neurosurgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands
- Maud Tjerkstra
- Brain Tumor Center Amsterdam, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands; Department of Neurosurgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands
- Cyra Leurs
- Department of Neurology, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands; MS Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands
- François Rustenburg
- Brain Tumor Center Amsterdam, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands; Department of Neurosurgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands
- Pepijn Schellen
- Brain Tumor Center Amsterdam, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands; Department of Neurosurgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands
- Heleen Verschueren
- Brain Tumor Center Amsterdam, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands; Department of Neurosurgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands
- Edward Post
- Brain Tumor Center Amsterdam, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands; Department of Neurosurgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands
- Kenn Zwaan
- Brain Tumor Center Amsterdam, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands; Department of Neurosurgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands
- Jip Ramaker
- Brain Tumor Center Amsterdam, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands; Department of Neurosurgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands
- Laurine E. Wedekind
- Brain Tumor Center Amsterdam, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands; Department of Neurosurgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands
- Jihane Tannous
- Department of Neurology, Massachusetts General Hospital and Neuroscience Program, Harvard Medical School, Boston, MA, USA
- Bauke Ylstra
- Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands
- Joep Killestein
- Department of Neurology, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands; MS Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands
- Farrah Mateen
- Department of Neurology, Massachusetts General Hospital and Neuroscience Program, Harvard Medical School, Boston, MA, USA
- Sander Idema
- Department of Neurosurgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands
- Philip C. de Witt Hamer
- Department of Neurosurgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands
- Anna C. Navis
- Department of Pathology, Radboud University Medical Center, Nijmegen, the Netherlands
- William P.J. Leenders
- Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands
- Ann Hoeben
- Department of Medical Oncology, Maastricht Academical Medical Center, Maastricht, the Netherlands
- Bastiaan Moraal
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands
- David P. Noske
- Brain Tumor Center Amsterdam, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands; Department of Neurosurgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands
- W. Peter Vandertop
- Brain Tumor Center Amsterdam, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands; Department of Neurosurgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands
- R. Jonas A. Nilsson
- Department of Neurosurgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands; Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden
- Bakhos A. Tannous
- Department of Neurology, Massachusetts General Hospital and Neuroscience Program, Harvard Medical School, Boston, MA, USA
- Pieter Wesseling
- Brain Tumor Center Amsterdam, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands; Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
- Jaap C. Reijneveld
- Brain Tumor Center Amsterdam, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands; Department of Neurology, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands
- Myron G. Best
- Brain Tumor Center Amsterdam, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands; Department of Neurosurgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands; Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands
- Thomas Wurdinger
- Brain Tumor Center Amsterdam, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands; Department of Neurosurgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands; Corresponding author
- Journal volume & issue
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Vol. 1,
no. 7
p. 100101
Abstract
Summary: Tumor-educated platelets (TEPs) are potential biomarkers for cancer diagnostics. We employ TEP-derived RNA panels, determined by swarm intelligence, to detect and monitor glioblastoma. We assessed specificity by comparing the spliced RNA profile of TEPs from glioblastoma patients with multiple sclerosis and brain metastasis patients (validation series, n = 157; accuracy, 80%; AUC, 0.81 [95% CI, 0.74–0.89; p < 0.001]). Second, analysis of patients with glioblastoma versus asymptomatic healthy controls in an independent validation series (n = 347) provided a detection accuracy of 95% and AUC of 0.97 (95% CI, 0.95–0.99; p < 0.001). Finally, we developed the digitalSWARM algorithm to improve monitoring of glioblastoma progression and demonstrate that the TEP tumor scores of individual glioblastoma patients represent tumor behavior and could be used to distinguish false positive progression from true progression (validation series, n = 20; accuracy, 85%; AUC, 0.86 [95% CI, 0.70–1.00; p < 0.012]). In conclusion, TEPs have potential as a minimally invasive biosource for blood-based diagnostics and monitoring of glioblastoma patients.