Detection and localization of early- and late-stage cancers using platelet RNA

Sjors G.J.G. In ’t Veld; Mohammad Arkani; Edward Post; Mafalda Antunes-Ferreira; Silvia D'Ambrosi; Daan C.L. Vessies; Lisa Vermunt; Adrienne Vancura; Mirte Muller; Anna Larissa N. Niemeijer; Jihane Tannous; Laura L. Meijer; Tessa Y.S. Le Large; Giulia Mantini; Niels E. Wondergem; Kimberley M. Heinhuis; Sandra van Wilpe; A. Josien Smits; Esther E.E. Drees; Eva Roos; Cyra E. Leurs; Lee Ann Tjon Kon Fat; Ewoud J. van der Lelij; Govert Dwarshuis; Maarten J. Kamphuis; Lisanne E. Visser; Romee Harting; Annemijn Gregory; Markus W. Schweiger; Laurine E. Wedekind; Jip Ramaker; Kenn Zwaan; Heleen Verschueren; Idris Bahce; Adrianus J. de Langen; Egbert F. Smit; Michel M. van den Heuvel; Koen J. Hartemink; Marijke J.E. Kuijpers; Mirjam G.A. oude Egbrink; Arjan W. Griffioen; Rafael Rossel; T. Jeroen N. Hiltermann; Elizabeth Lee-Lewandrowski; Kent B. Lewandrowski; Philip C. De Witt Hamer; Mathilde Kouwenhoven; Jaap C. Reijneveld; William P.J. Leenders; Ann Hoeben; Irma M. Verdonck-de Leeuw; C. René Leemans; Robert J. Baatenburg de Jong; Chris H.J. Terhaard; Robert P. Takes; Johannes A. Langendijk; Saskia C. de Jager; Adriaan O. Kraaijeveld; Gerard Pasterkamp; Minke Smits; Jack A. Schalken; Sylwia Łapińska-Szumczyk; Anna Łojkowska; Anna J. Żaczek; Henk Lokhorst; Niels W.C.J. van de Donk; Inger Nijhof; Henk Jan Prins; Josée M. Zijlstra; Sander Idema; Johannes C. Baayen; Charlotte E. Teunissen; Joep Killestein; Marc G. Besselink; Lindsay Brammen; Thomas Bachleitner-Hofmann; Farrah Mateen; John T.M. Plukker; Michal Heger; Quirijn de Mast; Ton Lisman; D. Michiel Pegtel; Harm Jan Bogaard; Jacek Jassem; Anna Supernat; Niven Mehra; Winald Gerritsen; Cornelis D. de Kroon; Christianne A.R. Lok; Jurgen M.J. Piek; Neeltje Steeghs; Winan J. van Houdt; Ruud H. Brakenhoff; Gabe S. Sonke; Henk M. Verheul; Elisa Giovannetti; Geert Kazemier; Siamack Sabrkhany; Ed Schuuring; Erik A. Sistermans; Rob Wolthuis; Hanne Meijers-Heijboer; Josephine Dorsman; Cees Oudejans; Bauke Ylstra; Bart A. Westerman; Daan van den Broek; Danijela Koppers-Lalic; Pieter Wesseling; R. Jonas A. Nilsson; W. Peter Vandertop; David P. Noske; Bakhos A. Tannous; Nik Sol; Myron G. Best; Thomas Wurdinger

doi:10.1016/j.ccell.2022.08.006

Detection and localization of early- and late-stage cancers using platelet RNA

Sjors G.J.G. In ’t Veld, Mohammad Arkani, Edward Post, Mafalda Antunes-Ferreira, Silvia D'Ambrosi, Daan C.L. Vessies, Lisa Vermunt, Adrienne Vancura, Mirte Muller, Anna Larissa N. Niemeijer, Jihane Tannous, Laura L. Meijer, Tessa Y.S. Le Large, Giulia Mantini, Niels E. Wondergem, Kimberley M. Heinhuis, Sandra van Wilpe, A. Josien Smits, Esther E.E. Drees, Eva RoosCyra E. Leurs, Lee Ann Tjon Kon Fat, Ewoud J. van der Lelij, Govert Dwarshuis, Maarten J. Kamphuis, Lisanne E. Visser, Romee Harting, Annemijn Gregory, Markus W. Schweiger, Laurine E. Wedekind, Jip Ramaker, Kenn Zwaan, Heleen Verschueren, Idris Bahce, Adrianus J. de Langen, Egbert F. Smit, Michel M. van den Heuvel, Koen J. Hartemink, Marijke J.E. Kuijpers, Mirjam G.A. oude Egbrink, Arjan W. Griffioen, Rafael Rossel, T. Jeroen N. Hiltermann, Elizabeth Lee-Lewandrowski, Kent B. Lewandrowski, Philip C. De Witt Hamer, Mathilde Kouwenhoven, Jaap C. Reijneveld, William P.J. Leenders, Ann Hoeben, Irma M. Verdonck-de Leeuw, C. René Leemans, Robert J. Baatenburg de Jong, Chris H.J. Terhaard, Robert P. Takes, Johannes A. Langendijk, Saskia C. de Jager, Adriaan O. Kraaijeveld, Gerard Pasterkamp, Minke Smits, Jack A. Schalken, Sylwia Łapińska-Szumczyk, Anna Łojkowska, Anna J. Żaczek, Henk Lokhorst, Niels W.C.J. van de Donk, Inger Nijhof, Henk Jan Prins, Josée M. Zijlstra, Sander Idema, Johannes C. Baayen, Charlotte E. Teunissen, Joep Killestein, Marc G. Besselink, Lindsay Brammen, Thomas Bachleitner-Hofmann, Farrah Mateen, John T.M. Plukker, Michal Heger, Quirijn de Mast, Ton Lisman, D. Michiel Pegtel, Harm Jan Bogaard, Jacek Jassem, Anna Supernat, Niven Mehra, Winald Gerritsen, Cornelis D. de Kroon, Christianne A.R. Lok, Jurgen M.J. Piek, Neeltje Steeghs, Winan J. van Houdt, Ruud H. Brakenhoff, Gabe S. Sonke, Henk M. Verheul, Elisa Giovannetti, Geert Kazemier, Siamack Sabrkhany, Ed Schuuring, Erik A. Sistermans, Rob Wolthuis, Hanne Meijers-Heijboer, Josephine Dorsman, Cees Oudejans, Bauke Ylstra, Bart A. Westerman, Daan van den Broek, Danijela Koppers-Lalic, Pieter Wesseling, R. Jonas A. Nilsson, W. Peter Vandertop, David P. Noske, Bakhos A. Tannous, Nik Sol, Myron G. Best^*, Thomas Wurdinger

^*Corresponding author for this work

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

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Abstract

Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening.

Original language	English
Pages (from-to)	999-1009.e6
Journal	Cancer Cell
Volume	40
Issue number	9
DOIs	https://doi.org/10.1016/j.ccell.2022.08.006
Publication status	Published - 12 Sept 2022

Bibliographical note

Acknowledgments:
We thank all the blood donors for their willingness to participate in this study. We are thankful to Krzysztof Pastuszak (Gdańsk University of Technology, Poland) for his feedback regarding data processing, the collaborators and the team of the NKI-AVL Core Facility Molecular Pathology and Biobanking (CFMPB) for supplying NKI-AVL Biobank material and lab support, the Amsterdam UMC Liquid Biopsy Center Core Facility, the Cancer Center Amsterdam Foundation, and Sebastiaan van de Sand (SIT B.V.) for computational resources. Financial support was provided by European Research Council 713727 and 336540 (T.W.), the Dutch Organisation of Scientific Research 91711366 (T.W.), Stichting STOPHersentumoren.nl (M.G. Best, N. Sol, T.W.), the Dutch Cancer Society (H.M.H. H.M.V. T.W. E.G. G.K. T.W.), the Bennink Foundation 2002262 (L.L.M. T.Y.S.L.L, E.G. G.K.), the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement 765492 (D.K.L. R.R. T.W.), the National Science Centre 2018/02/X/NZ5/01408 (A.S.), and the Medical University of Gdańsk statutory grant ST-23, 02-0023/07 (J.J.). In addition, this work was supported by the Netherlands Cardiovascular Research Initiative, an initiative with the support of the Dutch Heart Foundation (CVON2017-4 DOLPHIN-GENESIS, CVON2012-08 PHAEDRA; H-J.B.). Also, this study was carried out using the research infrastructure within the Netherlands Quality of Life and Biomedical Cohort Study in Head and Neck Cancer (NET-QUBIC) project funded by the Dutch Cancer Society/Alpe d'Huzes (grant VU-2013-5930). The funding bodies had no role in the design of the study or the collection, analysis, or interpretation of data nor in writing the manuscript. Conceptualization, S.G.J.G.I.t.V. N. Sol, M.G. Best, T.W.; funding acquisition, T.W. M.G. Best, N.S. H.M.H. H.M.V. E.G. G.K. L.L.M. T.Y.S.L.L. E.G. G.K. D.K.L. R.R. H-J.B.; resources, D.C.L.V. M.M. A-L.N.M. J.T. L.L.M. T.Y.S.L.L. G.M. N.E.W. K.M.H. S.v.W. A.J.S. E.E.E.D. E.R. C.E.L. L-A.T.K.F. I.B. A.J.d.L. E.F.S. M.M.v.d.H. K.J.H. M.J.E.K. M.G.A.o.E. A.W.G. R.R. T.J.N.H. E.L.L. K.B.L. P.C.d.W.H. M.K. J.C.R. W.P.J.L. A.H. I.M.V-d.L. C.R.L. R.J.B.d.J. C.H.J.T. R.P.T. J.A.L. S.C.d.J. A.O.K. G.P. M.S. J.A.S. S.Ł-S. A.Ł. A.J.Ż. H.L. N.W.C.J.v.d.D. I.N. H.J.P. J.M.Z. S.I. J.C.B. C.E.T. J.K. M.G. Besselink, L.B. T.B-H. F.M. J.T.M.P. M.H. Q.d.M. T.L. D.M.P. H-J.B. J.J. A.S. N.M. W.G. C.D.d.K. C.A.R.L. J.M.J.P. N. Steeghs, W.J.v.H. R.H.B. G.S.S. H.M.V. E.G. G.K. S.S. E.S. E.A.S. R.W. H.M-H. J.D. C.O. B.Y. B.A.W. D.v.d.B. D.K.L. P.W. R.J.A.N. W.P.V. D.P.N. B.A.T. N. Sol, M.G. Best; formal analysis (wet lab), E.P. M.A.F. S.D.A. A.V. M.J.K. L.E.V. R.H. A.G. M.W.S. L.E.W. J.R. K.Z. H.V. N. Sol, M.G. Best; formal analysis (dry lab), software, and data curation, S.G.J.G.I.t.V. E.P. N. Sol M.G. Best; methodology and visualization, S.G.J.G.I.t.V. M.A. E.P. M.A.F. S.D.A. L.V. E.J.v.d.L. G.D. N. Sol, M.G. Best, T.W.; writing – original draft, S.G.J.G.I.t.V, M.G. Best, T.W.; writing – review & editing, all authors. M.G. Best, R.J.A.N. and T.W. are inventors on relevant patent applications (PCT/NL2011/050518 and PCT/NL2018/050110). R.J.A.N. and T.W. are shareholders of Illumina, Inc. M.H. is chief formulation officer at Nurish.Me, Inc. and Camelina Sun LLC and has equity in those companies (whose business activities are unrelated to the present work). D.M.P. and D.K.L. are shareholders of ExBiome BV.

Publisher Copyright: © 2022 The Author(s)

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Cite this

In ’t Veld, S. G. J. G., Arkani, M., Post, E., Antunes-Ferreira, M., D'Ambrosi, S., Vessies, D. C. L., Vermunt, L., Vancura, A., Muller, M., Niemeijer, A. L. N., Tannous, J., Meijer, L. L., Le Large, T. Y. S., Mantini, G., Wondergem, N. E., Heinhuis, K. M., van Wilpe, S., Smits, A. J., Drees, E. E. E., ... Wurdinger, T. (2022). Detection and localization of early- and late-stage cancers using platelet RNA. Cancer Cell, 40(9), 999-1009.e6. https://doi.org/10.1016/j.ccell.2022.08.006

@article{520f8d829cf1469297f04dead1c68cfc,

title = "Detection and localization of early- and late-stage cancers using platelet RNA",

abstract = "Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening.",

author = "{In {\textquoteright}t Veld}, {Sjors G.J.G.} and Mohammad Arkani and Edward Post and Mafalda Antunes-Ferreira and Silvia D'Ambrosi and Vessies, {Daan C.L.} and Lisa Vermunt and Adrienne Vancura and Mirte Muller and Niemeijer, {Anna Larissa N.} and Jihane Tannous and Meijer, {Laura L.} and {Le Large}, {Tessa Y.S.} and Giulia Mantini and Wondergem, {Niels E.} and Heinhuis, {Kimberley M.} and {van Wilpe}, Sandra and Smits, {A. Josien} and Drees, {Esther E.E.} and Eva Roos and Leurs, {Cyra E.} and {Tjon Kon Fat}, {Lee Ann} and {van der Lelij}, {Ewoud J.} and Govert Dwarshuis and Kamphuis, {Maarten J.} and Visser, {Lisanne E.} and Romee Harting and Annemijn Gregory and Schweiger, {Markus W.} and Wedekind, {Laurine E.} and Jip Ramaker and Kenn Zwaan and Heleen Verschueren and Idris Bahce and {de Langen}, {Adrianus J.} and Smit, {Egbert F.} and {van den Heuvel}, {Michel M.} and Hartemink, {Koen J.} and Kuijpers, {Marijke J.E.} and {oude Egbrink}, {Mirjam G.A.} and Griffioen, {Arjan W.} and Rafael Rossel and Hiltermann, {T. Jeroen N.} and Elizabeth Lee-Lewandrowski and Lewandrowski, {Kent B.} and {De Witt Hamer}, {Philip C.} and Mathilde Kouwenhoven and Reijneveld, {Jaap C.} and Leenders, {William P.J.} and Ann Hoeben and {Verdonck-de Leeuw}, {Irma M.} and Leemans, {C. Ren{\'e}} and {Baatenburg de Jong}, {Robert J.} and Terhaard, {Chris H.J.} and Takes, {Robert P.} and Langendijk, {Johannes A.} and {de Jager}, {Saskia C.} and Kraaijeveld, {Adriaan O.} and Gerard Pasterkamp and Minke Smits and Schalken, {Jack A.} and Sylwia {\L}api{\'n}ska-Szumczyk and Anna {\L}ojkowska and {\.Z}aczek, {Anna J.} and Henk Lokhorst and {van de Donk}, {Niels W.C.J.} and Inger Nijhof and Prins, {Henk Jan} and Zijlstra, {Jos{\'e}e M.} and Sander Idema and Baayen, {Johannes C.} and Teunissen, {Charlotte E.} and Joep Killestein and Besselink, {Marc G.} and Lindsay Brammen and Thomas Bachleitner-Hofmann and Farrah Mateen and Plukker, {John T.M.} and Michal Heger and {de Mast}, Quirijn and Ton Lisman and Pegtel, {D. Michiel} and Bogaard, {Harm Jan} and Jacek Jassem and Anna Supernat and Niven Mehra and Winald Gerritsen and {de Kroon}, {Cornelis D.} and Lok, {Christianne A.R.} and Piek, {Jurgen M.J.} and Neeltje Steeghs and {van Houdt}, {Winan J.} and Brakenhoff, {Ruud H.} and Sonke, {Gabe S.} and Verheul, {Henk M.} and Elisa Giovannetti and Geert Kazemier and Siamack Sabrkhany and Ed Schuuring and Sistermans, {Erik A.} and Rob Wolthuis and Hanne Meijers-Heijboer and Josephine Dorsman and Cees Oudejans and Bauke Ylstra and Westerman, {Bart A.} and {van den Broek}, Daan and Danijela Koppers-Lalic and Pieter Wesseling and Nilsson, {R. Jonas A.} and Vandertop, {W. Peter} and Noske, {David P.} and Tannous, {Bakhos A.} and Nik Sol and Best, {Myron G.} and Thomas Wurdinger",

note = "Acknowledgments: We thank all the blood donors for their willingness to participate in this study. We are thankful to Krzysztof Pastuszak (Gda{\'n}sk University of Technology, Poland) for his feedback regarding data processing, the collaborators and the team of the NKI-AVL Core Facility Molecular Pathology and Biobanking (CFMPB) for supplying NKI-AVL Biobank material and lab support, the Amsterdam UMC Liquid Biopsy Center Core Facility, the Cancer Center Amsterdam Foundation, and Sebastiaan van de Sand (SIT B.V.) for computational resources. Financial support was provided by European Research Council 713727 and 336540 (T.W.), the Dutch Organisation of Scientific Research 91711366 (T.W.), Stichting STOPHersentumoren.nl (M.G. Best, N. Sol, T.W.), the Dutch Cancer Society (H.M.H. H.M.V. T.W. E.G. G.K. T.W.), the Bennink Foundation 2002262 (L.L.M. T.Y.S.L.L, E.G. G.K.), the European Union's Horizon 2020 research and innovation program under the Marie Sk{\l}odowska-Curie grant agreement 765492 (D.K.L. R.R. T.W.), the National Science Centre 2018/02/X/NZ5/01408 (A.S.), and the Medical University of Gda{\'n}sk statutory grant ST-23, 02-0023/07 (J.J.). In addition, this work was supported by the Netherlands Cardiovascular Research Initiative, an initiative with the support of the Dutch Heart Foundation (CVON2017-4 DOLPHIN-GENESIS, CVON2012-08 PHAEDRA; H-J.B.). Also, this study was carried out using the research infrastructure within the Netherlands Quality of Life and Biomedical Cohort Study in Head and Neck Cancer (NET-QUBIC) project funded by the Dutch Cancer Society/Alpe d'Huzes (grant VU-2013-5930). The funding bodies had no role in the design of the study or the collection, analysis, or interpretation of data nor in writing the manuscript. Conceptualization, S.G.J.G.I.t.V. N. Sol, M.G. Best, T.W.; funding acquisition, T.W. M.G. Best, N.S. H.M.H. H.M.V. E.G. G.K. L.L.M. T.Y.S.L.L. E.G. G.K. D.K.L. R.R. H-J.B.; resources, D.C.L.V. M.M. A-L.N.M. J.T. L.L.M. T.Y.S.L.L. G.M. N.E.W. K.M.H. S.v.W. A.J.S. E.E.E.D. E.R. C.E.L. L-A.T.K.F. I.B. A.J.d.L. E.F.S. M.M.v.d.H. K.J.H. M.J.E.K. M.G.A.o.E. A.W.G. R.R. T.J.N.H. E.L.L. K.B.L. P.C.d.W.H. M.K. J.C.R. W.P.J.L. A.H. I.M.V-d.L. C.R.L. R.J.B.d.J. C.H.J.T. R.P.T. J.A.L. S.C.d.J. A.O.K. G.P. M.S. J.A.S. S.{\L}-S. A.{\L}. A.J.{\.Z}. H.L. N.W.C.J.v.d.D. I.N. H.J.P. J.M.Z. S.I. J.C.B. C.E.T. J.K. M.G. Besselink, L.B. T.B-H. F.M. J.T.M.P. M.H. Q.d.M. T.L. D.M.P. H-J.B. J.J. A.S. N.M. W.G. C.D.d.K. C.A.R.L. J.M.J.P. N. Steeghs, W.J.v.H. R.H.B. G.S.S. H.M.V. E.G. G.K. S.S. E.S. E.A.S. R.W. H.M-H. J.D. C.O. B.Y. B.A.W. D.v.d.B. D.K.L. P.W. R.J.A.N. W.P.V. D.P.N. B.A.T. N. Sol, M.G. Best; formal analysis (wet lab), E.P. M.A.F. S.D.A. A.V. M.J.K. L.E.V. R.H. A.G. M.W.S. L.E.W. J.R. K.Z. H.V. N. Sol, M.G. Best; formal analysis (dry lab), software, and data curation, S.G.J.G.I.t.V. E.P. N. Sol M.G. Best; methodology and visualization, S.G.J.G.I.t.V. M.A. E.P. M.A.F. S.D.A. L.V. E.J.v.d.L. G.D. N. Sol, M.G. Best, T.W.; writing – original draft, S.G.J.G.I.t.V, M.G. Best, T.W.; writing – review & editing, all authors. M.G. Best, R.J.A.N. and T.W. are inventors on relevant patent applications (PCT/NL2011/050518 and PCT/NL2018/050110). R.J.A.N. and T.W. are shareholders of Illumina, Inc. M.H. is chief formulation officer at Nurish.Me, Inc. and Camelina Sun LLC and has equity in those companies (whose business activities are unrelated to the present work). D.M.P. and D.K.L. are shareholders of ExBiome BV. Publisher Copyright: {\textcopyright} 2022 The Author(s)",

year = "2022",

month = sep,

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doi = "10.1016/j.ccell.2022.08.006",

language = "English",

volume = "40",

pages = "999--1009.e6",

journal = "Cancer Cell",

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number = "9",

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In ’t Veld, SGJG, Arkani, M, Post, E, Antunes-Ferreira, M, D'Ambrosi, S, Vessies, DCL, Vermunt, L, Vancura, A, Muller, M, Niemeijer, ALN, Tannous, J, Meijer, LL, Le Large, TYS, Mantini, G, Wondergem, NE, Heinhuis, KM, van Wilpe, S, Smits, AJ, Drees, EEE, Roos, E, Leurs, CE, Tjon Kon Fat, LA, van der Lelij, EJ, Dwarshuis, G, Kamphuis, MJ, Visser, LE, Harting, R, Gregory, A, Schweiger, MW, Wedekind, LE, Ramaker, J, Zwaan, K, Verschueren, H, Bahce, I, de Langen, AJ, Smit, EF, van den Heuvel, MM, Hartemink, KJ, Kuijpers, MJE, oude Egbrink, MGA, Griffioen, AW, Rossel, R, Hiltermann, TJN, Lee-Lewandrowski, E, Lewandrowski, KB, De Witt Hamer, PC, Kouwenhoven, M, Reijneveld, JC, Leenders, WPJ, Hoeben, A, Verdonck-de Leeuw, IM, Leemans, CR, Baatenburg de Jong, RJ, Terhaard, CHJ, Takes, RP, Langendijk, JA, de Jager, SC, Kraaijeveld, AO, Pasterkamp, G, Smits, M, Schalken, JA, Łapińska-Szumczyk, S, Łojkowska, A, Żaczek, AJ, Lokhorst, H, van de Donk, NWCJ, Nijhof, I, Prins, HJ, Zijlstra, JM, Idema, S, Baayen, JC, Teunissen, CE, Killestein, J, Besselink, MG, Brammen, L, Bachleitner-Hofmann, T, Mateen, F, Plukker, JTM, Heger, M, de Mast, Q, Lisman, T, Pegtel, DM, Bogaard, HJ, Jassem, J, Supernat, A, Mehra, N, Gerritsen, W, de Kroon, CD, Lok, CAR, Piek, JMJ, Steeghs, N, van Houdt, WJ, Brakenhoff, RH, Sonke, GS, Verheul, HM, Giovannetti, E, Kazemier, G, Sabrkhany, S, Schuuring, E, Sistermans, EA, Wolthuis, R, Meijers-Heijboer, H, Dorsman, J, Oudejans, C, Ylstra, B, Westerman, BA, van den Broek, D, Koppers-Lalic, D, Wesseling, P, Nilsson, RJA, Vandertop, WP, Noske, DP, Tannous, BA, Sol, N, Best, MG & Wurdinger, T 2022, 'Detection and localization of early- and late-stage cancers using platelet RNA', Cancer Cell, vol. 40, no. 9, pp. 999-1009.e6. https://doi.org/10.1016/j.ccell.2022.08.006

TY - JOUR

T1 - Detection and localization of early- and late-stage cancers using platelet RNA

AU - In ’t Veld, Sjors G.J.G.

AU - Arkani, Mohammad

AU - Post, Edward

AU - Antunes-Ferreira, Mafalda

AU - D'Ambrosi, Silvia

AU - Vessies, Daan C.L.

AU - Vermunt, Lisa

AU - Vancura, Adrienne

AU - Muller, Mirte

AU - Niemeijer, Anna Larissa N.

AU - Tannous, Jihane

AU - Meijer, Laura L.

AU - Le Large, Tessa Y.S.

AU - Mantini, Giulia

AU - Wondergem, Niels E.

AU - Heinhuis, Kimberley M.

AU - van Wilpe, Sandra

AU - Smits, A. Josien

AU - Drees, Esther E.E.

AU - Roos, Eva

AU - Leurs, Cyra E.

AU - Tjon Kon Fat, Lee Ann

AU - van der Lelij, Ewoud J.

AU - Dwarshuis, Govert

AU - Kamphuis, Maarten J.

AU - Visser, Lisanne E.

AU - Harting, Romee

AU - Gregory, Annemijn

AU - Schweiger, Markus W.

AU - Wedekind, Laurine E.

AU - Ramaker, Jip

AU - Zwaan, Kenn

AU - Verschueren, Heleen

AU - Bahce, Idris

AU - de Langen, Adrianus J.

AU - Smit, Egbert F.

AU - van den Heuvel, Michel M.

AU - Hartemink, Koen J.

AU - Kuijpers, Marijke J.E.

AU - oude Egbrink, Mirjam G.A.

AU - Griffioen, Arjan W.

AU - Rossel, Rafael

AU - Hiltermann, T. Jeroen N.

AU - Lee-Lewandrowski, Elizabeth

AU - Lewandrowski, Kent B.

AU - De Witt Hamer, Philip C.

AU - Kouwenhoven, Mathilde

AU - Reijneveld, Jaap C.

AU - Leenders, William P.J.

AU - Hoeben, Ann

AU - Verdonck-de Leeuw, Irma M.

AU - Leemans, C. René

AU - Baatenburg de Jong, Robert J.

AU - Terhaard, Chris H.J.

AU - Takes, Robert P.

AU - Langendijk, Johannes A.

AU - de Jager, Saskia C.

AU - Kraaijeveld, Adriaan O.

AU - Pasterkamp, Gerard

AU - Smits, Minke

AU - Schalken, Jack A.

AU - Łapińska-Szumczyk, Sylwia

AU - Łojkowska, Anna

AU - Żaczek, Anna J.

AU - Lokhorst, Henk

AU - van de Donk, Niels W.C.J.

AU - Nijhof, Inger

AU - Prins, Henk Jan

AU - Zijlstra, Josée M.

AU - Idema, Sander

AU - Baayen, Johannes C.

AU - Teunissen, Charlotte E.

AU - Killestein, Joep

AU - Besselink, Marc G.

AU - Brammen, Lindsay

AU - Bachleitner-Hofmann, Thomas

AU - Mateen, Farrah

AU - Plukker, John T.M.

AU - Heger, Michal

AU - de Mast, Quirijn

AU - Lisman, Ton

AU - Pegtel, D. Michiel

AU - Bogaard, Harm Jan

AU - Jassem, Jacek

AU - Supernat, Anna

AU - Mehra, Niven

AU - Gerritsen, Winald

AU - de Kroon, Cornelis D.

AU - Lok, Christianne A.R.

AU - Piek, Jurgen M.J.

AU - Steeghs, Neeltje

AU - van Houdt, Winan J.

AU - Brakenhoff, Ruud H.

AU - Sonke, Gabe S.

AU - Verheul, Henk M.

AU - Giovannetti, Elisa

AU - Kazemier, Geert

AU - Sabrkhany, Siamack

AU - Schuuring, Ed

AU - Sistermans, Erik A.

AU - Wolthuis, Rob

AU - Meijers-Heijboer, Hanne

AU - Dorsman, Josephine

AU - Oudejans, Cees

AU - Ylstra, Bauke

AU - Westerman, Bart A.

AU - van den Broek, Daan

AU - Koppers-Lalic, Danijela

AU - Wesseling, Pieter

AU - Nilsson, R. Jonas A.

AU - Vandertop, W. Peter

AU - Noske, David P.

AU - Tannous, Bakhos A.

AU - Sol, Nik

AU - Best, Myron G.

AU - Wurdinger, Thomas

N1 - Acknowledgments: We thank all the blood donors for their willingness to participate in this study. We are thankful to Krzysztof Pastuszak (Gdańsk University of Technology, Poland) for his feedback regarding data processing, the collaborators and the team of the NKI-AVL Core Facility Molecular Pathology and Biobanking (CFMPB) for supplying NKI-AVL Biobank material and lab support, the Amsterdam UMC Liquid Biopsy Center Core Facility, the Cancer Center Amsterdam Foundation, and Sebastiaan van de Sand (SIT B.V.) for computational resources. Financial support was provided by European Research Council 713727 and 336540 (T.W.), the Dutch Organisation of Scientific Research 91711366 (T.W.), Stichting STOPHersentumoren.nl (M.G. Best, N. Sol, T.W.), the Dutch Cancer Society (H.M.H. H.M.V. T.W. E.G. G.K. T.W.), the Bennink Foundation 2002262 (L.L.M. T.Y.S.L.L, E.G. G.K.), the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement 765492 (D.K.L. R.R. T.W.), the National Science Centre 2018/02/X/NZ5/01408 (A.S.), and the Medical University of Gdańsk statutory grant ST-23, 02-0023/07 (J.J.). In addition, this work was supported by the Netherlands Cardiovascular Research Initiative, an initiative with the support of the Dutch Heart Foundation (CVON2017-4 DOLPHIN-GENESIS, CVON2012-08 PHAEDRA; H-J.B.). Also, this study was carried out using the research infrastructure within the Netherlands Quality of Life and Biomedical Cohort Study in Head and Neck Cancer (NET-QUBIC) project funded by the Dutch Cancer Society/Alpe d'Huzes (grant VU-2013-5930). The funding bodies had no role in the design of the study or the collection, analysis, or interpretation of data nor in writing the manuscript. Conceptualization, S.G.J.G.I.t.V. N. Sol, M.G. Best, T.W.; funding acquisition, T.W. M.G. Best, N.S. H.M.H. H.M.V. E.G. G.K. L.L.M. T.Y.S.L.L. E.G. G.K. D.K.L. R.R. H-J.B.; resources, D.C.L.V. M.M. A-L.N.M. J.T. L.L.M. T.Y.S.L.L. G.M. N.E.W. K.M.H. S.v.W. A.J.S. E.E.E.D. E.R. C.E.L. L-A.T.K.F. I.B. A.J.d.L. E.F.S. M.M.v.d.H. K.J.H. M.J.E.K. M.G.A.o.E. A.W.G. R.R. T.J.N.H. E.L.L. K.B.L. P.C.d.W.H. M.K. J.C.R. W.P.J.L. A.H. I.M.V-d.L. C.R.L. R.J.B.d.J. C.H.J.T. R.P.T. J.A.L. S.C.d.J. A.O.K. G.P. M.S. J.A.S. S.Ł-S. A.Ł. A.J.Ż. H.L. N.W.C.J.v.d.D. I.N. H.J.P. J.M.Z. S.I. J.C.B. C.E.T. J.K. M.G. Besselink, L.B. T.B-H. F.M. J.T.M.P. M.H. Q.d.M. T.L. D.M.P. H-J.B. J.J. A.S. N.M. W.G. C.D.d.K. C.A.R.L. J.M.J.P. N. Steeghs, W.J.v.H. R.H.B. G.S.S. H.M.V. E.G. G.K. S.S. E.S. E.A.S. R.W. H.M-H. J.D. C.O. B.Y. B.A.W. D.v.d.B. D.K.L. P.W. R.J.A.N. W.P.V. D.P.N. B.A.T. N. Sol, M.G. Best; formal analysis (wet lab), E.P. M.A.F. S.D.A. A.V. M.J.K. L.E.V. R.H. A.G. M.W.S. L.E.W. J.R. K.Z. H.V. N. Sol, M.G. Best; formal analysis (dry lab), software, and data curation, S.G.J.G.I.t.V. E.P. N. Sol M.G. Best; methodology and visualization, S.G.J.G.I.t.V. M.A. E.P. M.A.F. S.D.A. L.V. E.J.v.d.L. G.D. N. Sol, M.G. Best, T.W.; writing – original draft, S.G.J.G.I.t.V, M.G. Best, T.W.; writing – review & editing, all authors. M.G. Best, R.J.A.N. and T.W. are inventors on relevant patent applications (PCT/NL2011/050518 and PCT/NL2018/050110). R.J.A.N. and T.W. are shareholders of Illumina, Inc. M.H. is chief formulation officer at Nurish.Me, Inc. and Camelina Sun LLC and has equity in those companies (whose business activities are unrelated to the present work). D.M.P. and D.K.L. are shareholders of ExBiome BV. Publisher Copyright: © 2022 The Author(s)

PY - 2022/9/12

Y1 - 2022/9/12

N2 - Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening.

AB - Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening.

UR - http://www.scopus.com/inward/record.url?scp=85137385164&partnerID=8YFLogxK

U2 - 10.1016/j.ccell.2022.08.006

DO - 10.1016/j.ccell.2022.08.006

M3 - Article

C2 - 36055228

AN - SCOPUS:85137385164

SN - 1535-6108

VL - 40

SP - 999-1009.e6

JO - Cancer Cell

JF - Cancer Cell

IS - 9

ER -

Detection and localization of early- and late-stage cancers using platelet RNA

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