RNA-Seq of Tumor-Educated Platelets Enables Blood-Based Pan-Cancer, Multiclass, and Molecular Pathway Cancer Diagnostics.
Myron G Best, Nik Sol, Irsan Kooi, Jihane Tannous, Bart A Westerman, François Rustenburg, Pepijn Schellen, Heleen Verschueren, Edward Post, Jan Koster, Bauke Ylstra, Najim Ameziane, Josephine Dorsman, Egbert F Smit, Henk M Verheul, David P Noske, Jaap C Reijneveld, R Jonas A Nilsson, Bakhos A Tannous, Pieter Wesseling, Thomas Wurdinger
Author Information
Myron G Best: Department of Pathology, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands; Department of Neurosurgery, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.
Nik Sol: Department of Neurology, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.
Irsan Kooi: Department of Clinical Genetics, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.
Jihane Tannous: Department of Neurology, Massachusetts General Hospital and Neuroscience Program, Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA.
Bart A Westerman: Department of Neurosurgery, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.
François Rustenburg: Department of Pathology, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands; Department of Neurosurgery, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.
Pepijn Schellen: Department of Neurosurgery, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands; thromboDx B.V., 1098 EA Amsterdam, the Netherlands.
Heleen Verschueren: Department of Neurosurgery, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands; thromboDx B.V., 1098 EA Amsterdam, the Netherlands.
Edward Post: Department of Neurosurgery, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands; thromboDx B.V., 1098 EA Amsterdam, the Netherlands.
Jan Koster: Department of Oncogenomics, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
Bauke Ylstra: Department of Pathology, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.
Najim Ameziane: Department of Clinical Genetics, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.
Josephine Dorsman: Department of Clinical Genetics, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.
Egbert F Smit: Department of Pulmonary Diseases, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.
Henk M Verheul: Department of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.
David P Noske: Department of Neurosurgery, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.
Jaap C Reijneveld: Department of Neurology, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.
R Jonas A Nilsson: Department of Neurosurgery, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands; thromboDx B.V., 1098 EA Amsterdam, the Netherlands; Department of Radiation Sciences, Oncology, Umeå University, 90185 Umeå, Sweden.
Bakhos A Tannous: Department of Neurology, Massachusetts General Hospital and Neuroscience Program, Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA.
Pieter Wesseling: Department of Pathology, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands; Department of Pathology, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands.
Thomas Wurdinger: Department of Neurosurgery, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands; Department of Neurology, Massachusetts General Hospital and Neuroscience Program, Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA; thromboDx B.V., 1098 EA Amsterdam, the Netherlands. Electronic address: t.wurdinger@vumc.nl.
Tumor-educated blood platelets (TEPs) are implicated as central players in the systemic and local responses to tumor growth, thereby altering their RNA profile. We determined the diagnostic potential of TEPs by mRNA sequencing of 283 platelet samples. We distinguished 228 patients with localized and metastasized tumors from 55 healthy individuals with 96% accuracy. Across six different tumor types, the location of the primary tumor was correctly identified with 71% accuracy. Also, MET or HER2-positive, and mutant KRAS, EGFR, or PIK3CA tumors were accurately distinguished using surrogate TEP mRNA profiles. Our results indicate that blood platelets provide a valuable platform for pan-cancer, multiclass cancer, and companion diagnostics, possibly enabling clinical advances in blood-based "liquid biopsies".
