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

doi:10.1016/j.ccell.2015.09.018

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

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

Authors

Myron G Best¹, Nik Sol², Irsan Kooi³, Jihane Tannous⁴, Bart A Westerman⁵, François Rustenburg¹, Pepijn Schellen⁶, Heleen Verschueren⁶, Edward Post⁶, Jan Koster⁷, Bauke Ylstra⁸, Najim Ameziane³, Josephine Dorsman³, Egbert F Smit⁹, Henk M Verheul¹⁰, David P Noske⁵, Jaap C Reijneveld², R Jonas A Nilsson¹¹, Bakhos A Tannous⁴, Pieter Wesseling¹², Thomas Wurdinger¹³

Affiliations

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".

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Biomarkers, Tumor / blood
Biomarkers, Tumor / genetics*
Blood Platelets / metabolism*
Class I Phosphatidylinositol 3-Kinases
ErbB Receptors / genetics
Female
Gene Expression Profiling / methods
Gene Ontology
Humans
Male
Middle Aged
Mutation
Neoplasms / blood
Neoplasms / diagnosis
Neoplasms / genetics*
Pathology, Molecular / methods
Phosphatidylinositol 3-Kinases / genetics
Proto-Oncogene Proteins c-met / genetics
Proto-Oncogene Proteins p21(ras) / genetics
Receptor, ErbB-2 / genetics
Reproducibility of Results
Sensitivity and Specificity
Sequence Analysis, RNA / methods
Signal Transduction / genetics*
Support Vector Machine
Young Adult

Substances

Biomarkers, Tumor
KRAS protein, human
Phosphatidylinositol 3-Kinases
Class I Phosphatidylinositol 3-Kinases
PIK3CA protein, human
EGFR protein, human
ErbB Receptors
MET protein, human
Proto-Oncogene Proteins c-met
Receptor, ErbB-2
Proto-Oncogene Proteins p21(ras)

Associated data

GEO/GSE68086

Abstract

Publication types

MeSH terms

Substances

Associated data

Grants and funding