title: RNA-Seq of Tumor-Educated Platelets Enables Blood-Based Pan-Cancer, Multiclass, and Molecular Pathway Cancer Diagnostics.
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".
authors.affiliation: 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.
authors.forename: Myron G
authors.initials: MG
authors.lastname: Best
authors.affiliation: Department of Neurology, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.
authors.forename: Nik
authors.initials: N
authors.lastname: Sol
authors.affiliation: Department of Clinical Genetics, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.
authors.forename: Irsan
authors.initials: I
authors.lastname: Kooi
authors.affiliation: Department of Neurology, Massachusetts General Hospital and Neuroscience Program, Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA.
authors.forename: Jihane
authors.initials: J
authors.lastname: Tannous
authors.affiliation: Department of Neurosurgery, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.
authors.forename: Bart A
authors.initials: BA
authors.lastname: Westerman
authors.affiliation: 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.
authors.forename: François
authors.initials: F
authors.lastname: Rustenburg
authors.affiliation: 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.
authors.forename: Pepijn
authors.initials: P
authors.lastname: Schellen
authors.affiliation: 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.
authors.forename: Heleen
authors.initials: H
authors.lastname: Verschueren
authors.affiliation: 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.
authors.forename: Edward
authors.initials: E
authors.lastname: Post
authors.affiliation: Department of Oncogenomics, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Koster
authors.affiliation: Department of Pathology, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.
authors.forename: Bauke
authors.initials: B
authors.lastname: Ylstra
authors.affiliation: Department of Clinical Genetics, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.
authors.forename: Najim
authors.initials: N
authors.lastname: Ameziane
authors.affiliation: Department of Clinical Genetics, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.
authors.forename: Josephine
authors.initials: J
authors.lastname: Dorsman
authors.affiliation: Department of Pulmonary Diseases, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.
authors.forename: Egbert F
authors.initials: EF
authors.lastname: Smit
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.
authors.forename: Henk M
authors.initials: HM
authors.lastname: Verheul
authors.affiliation: Department of Neurosurgery, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.
authors.forename: David P
authors.initials: DP
authors.lastname: Noske
authors.affiliation: Department of Neurology, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.
authors.forename: Jaap C
authors.initials: JC
authors.lastname: Reijneveld
authors.affiliation: 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.
authors.forename: R Jonas A
authors.initials: RJA
authors.lastname: Nilsson
authors.affiliation: Department of Neurology, Massachusetts General Hospital and Neuroscience Program, Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA.
authors.forename: Bakhos A
authors.initials: BA
authors.lastname: Tannous
authors.affiliation: 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.
authors.forename: Pieter
authors.initials: P
authors.lastname: Wesseling
authors.affiliation: 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.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wurdinger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D001792:Blood Platelets / Q000378:metabolism*; D058534:Class I Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D063990:Gene Ontology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009369:Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D057089:Pathology, Molecular / Q000379:methods; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D017423:Sequence Analysis, RNA / Q000379:methods; D015398:Signal Transduction / Q000235:genetics*; D060388:Support Vector Machine; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D058534:Class I Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D019869:Phosphatidylinositol 3-Kinases; D019859:Proto-Oncogene Proteins c-met; D016283:Proto-Oncogene Proteins p21(ras); D018719:Erb-b2 Receptor Tyrosine Kinases; C117307:KRAS protein, human; C484760:PIK3CA protein, human; C512478:EGFR protein, human; C491743:MET protein, human