Cancer Cell. 2015 Nov 9;28(5):666-676. doi: 10.1016/j.ccell.2015.09.018. Epub 2015 Oct 29.

RNA-Seq of Tumor-Educated Platelets Enables Blood-Based Pan-Cancer, Multiclass, and Molecular Pathway Cancer Diagnostics.

Best MG¹, Sol N², Kooi I³, Tannous J⁴, Westerman BA⁵, Rustenburg F¹, Schellen P⁶, Verschueren H⁶, Post E⁶, Koster J⁷, Ylstra B⁸, Ameziane N³, Dorsman J³, Smit EF⁹, Verheul HM¹⁰, Noske DP⁵, Reijneveld JC², Nilsson RJA¹¹, Tannous BA⁴, Wesseling P¹², Wurdinger T¹³.

Author information

1: 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.
2: Department of Neurology, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.
3: Department of Clinical Genetics, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.
4: Department of Neurology, Massachusetts General Hospital and Neuroscience Program, Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA.
5: Department of Neurosurgery, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.
6: 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.
7: Department of Oncogenomics, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
8: Department of Pathology, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.
9: Department of Pulmonary Diseases, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.
10: Department of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.
11: 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.
12: 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.
13: 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.

Abstract

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".