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

M.G. Best; N. Sol; E.I. Kooi; J. Tannous; A. Westerman; F. Rustenburg; P. Schellen; H. Verschueren; E. Post; J. Koster; B. Ylstra; N. Ameziane; J. Dorsman; E.F. Smit; H.M. Verheul; D.P. Noske; J.C. Reijneveld; R.J.A. Nilsson; B.A. Tannous; P. Wesseling; T. Wurdinger

doi:https://doi.org/10.1016/j.ccell.2015.09.018

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

M.G. Best, N. Sol, E.I. Kooi, J. Tannous, A. Westerman, F. Rustenburg, P. Schellen, H. Verschueren, E. Post, J. Koster, B. Ylstra, N. Ameziane, J. Dorsman, E.F. Smit, H.M. Verheul, D.P. Noske, J.C. Reijneveld, R.J.A. Nilsson, B.A. Tannous, P. WesselingT. Wurdinger

Research output: Contribution to journal › Article › Academic › peer-review

620 Citations (Scopus)

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".

Original language	English
Pages (from-to)	666-676
Number of pages	11
Journal	Cancer cell
Volume	28
Issue number	5
DOIs	https://doi.org/10.1016/j.ccell.2015.09.018
Publication status	Published - 9 Nov 2015

Keywords

Adult
Aged
Aged, 80 and over
Biomarkers, Tumor/blood
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
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

Access to Document

https://doi.org/10.1016/j.ccell.2015.09.018

Cite this

Best, M. G., Sol, N., Kooi, E. I., Tannous, J., Westerman, A., Rustenburg, F., Schellen, P., Verschueren, H., Post, E., Koster, J., Ylstra, B., Ameziane, N., Dorsman, J., Smit, E. F., Verheul, H. M., Noske, D. P., Reijneveld, J. C., Nilsson, R. J. A., Tannous, B. A., ... Wurdinger, T. (2015). RNA-Seq of Tumor-Educated Platelets Enables Blood-Based Pan-Cancer, Multiclass, and Molecular Pathway Cancer Diagnostics. Cancer cell, 28(5), 666-676. https://doi.org/10.1016/j.ccell.2015.09.018

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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{"}. ",

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author = "M.G. Best and N. Sol and E.I. Kooi and J. Tannous and A. Westerman and F. Rustenburg and P. Schellen and H. Verschueren and E. Post and J. Koster and B. Ylstra and N. Ameziane and J. Dorsman and E.F. Smit and H.M. Verheul and D.P. Noske and J.C. Reijneveld and R.J.A. Nilsson and B.A. Tannous and P. Wesseling and T. Wurdinger",

year = "2015",

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doi = "https://doi.org/10.1016/j.ccell.2015.09.018",

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Best, MG , Sol, N, Kooi, EI, Tannous, J, Westerman, A, Rustenburg, F, Schellen, P, Verschueren, H, Post, E, Koster, J , Ylstra, B, Ameziane, N, Dorsman, J, Smit, EF, Verheul, HM, Noske, DP , Reijneveld, JC, Nilsson, RJA, Tannous, BA, Wesseling, P & Wurdinger, T 2015, 'RNA-Seq of Tumor-Educated Platelets Enables Blood-Based Pan-Cancer, Multiclass, and Molecular Pathway Cancer Diagnostics', Cancer cell, vol. 28, no. 5, pp. 666-676. https://doi.org/10.1016/j.ccell.2015.09.018

TY - JOUR

T1 - RNA-Seq of Tumor-Educated Platelets Enables Blood-Based Pan-Cancer, Multiclass, and Molecular Pathway Cancer Diagnostics

AU - Best, M.G.

AU - Sol, N.

AU - Kooi, E.I.

AU - Tannous, J.

AU - Westerman, A.

AU - Rustenburg, F.

AU - Schellen, P.

AU - Verschueren, H.

AU - Post, E.

AU - Koster, J.

AU - Ylstra, B.

AU - Ameziane, N.

AU - Dorsman, J.

AU - Smit, E.F.

AU - Verheul, H.M.

AU - Noske, D.P.

AU - Reijneveld, J.C.

AU - Nilsson, R.J.A.

AU - Tannous, B.A.

AU - Wesseling, P.

AU - Wurdinger, T.

PY - 2015/11/9

Y1 - 2015/11/9

N2 - 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".

AB - 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".

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Biomarkers, Tumor/blood

KW - Blood Platelets/metabolism

KW - Class I Phosphatidylinositol 3-Kinases

KW - ErbB Receptors/genetics

KW - Female

KW - Gene Expression Profiling/methods

KW - Gene Ontology

KW - Humans

KW - Male

KW - Middle Aged

KW - Mutation

KW - Neoplasms/blood

KW - Pathology, Molecular/methods

KW - Phosphatidylinositol 3-Kinases/genetics

KW - Proto-Oncogene Proteins c-met/genetics

KW - Proto-Oncogene Proteins p21(ras)/genetics

KW - Receptor, ErbB-2/genetics

KW - Reproducibility of Results

KW - Sensitivity and Specificity

KW - Sequence Analysis, RNA/methods

KW - Signal Transduction/genetics

KW - Support Vector Machine

KW - Young Adult

U2 - https://doi.org/10.1016/j.ccell.2015.09.018

DO - https://doi.org/10.1016/j.ccell.2015.09.018

M3 - Article

C2 - 26525104

SN - 1535-6108

VL - 28

SP - 666

EP - 676

JO - Cancer cell

JF - Cancer cell

IS - 5

ER -