Detection and localization of early- and late-stage cancers using platelet RNA
In ’t Veld, Sjors G.J.G.; Arkani, Mohammad; Post, Edward; Antunes-Ferreira, Mafalda; D'Ambrosi, Silvia; Vessies, Daan C.L.; Vermunt, Lisa; Vancura, Adrienne; Muller, Mirte; Niemeijer, Anna Larissa N.; Tannous, Jihane; Meijer, Laura L.; Le Large, Tessa Y.S.; Mantini, Giulia; Wondergem, Niels E.; Heinhuis, Kimberley M.; van Wilpe, Sandra; Smits, A. Josien; Drees, Esther E.E.; Roos, Eva; Leurs, Cyra E.; Tjon Kon Fat, Lee Ann; van der Lelij, Ewoud J.; Dwarshuis, Govert; Kamphuis, Maarten J.; Visser, Lisanne E.; Harting, Romee; Gregory, Annemijn; Schweiger, Markus W.; Wedekind, Laurine E.; Ramaker, Jip; Zwaan, Kenn; Verschueren, Heleen; Bahce, Idris; de Langen, Adrianus J.; Smit, Egbert F.; van den Heuvel, Michel M.; Hartemink, Koen J.; Kuijpers, Marijke J.E.; oude Egbrink, Mirjam G.A.; Griffioen, Arjan W.; Rossel, Rafael; Hiltermann, T. Jeroen N.; Lee-Lewandrowski, Elizabeth; Lewandrowski, Kent B.; De Witt Hamer, Philip C.; Kouwenhoven, Mathilde; Reijneveld, Jaap C.; Leenders, William P.J.; Hoeben, Ann; Verdonck-de Leeuw, Irma M.; Leemans, C. René; Baatenburg de Jong, Robert J.; Terhaard, Chris H.J.; Takes, Robert P.; Langendijk, Johannes A.; de Jager, Saskia C.; Kraaijeveld, Adriaan O.; Pasterkamp, Gerard; Smits, Minke; Schalken, Jack A.; Łapińska-Szumczyk, Sylwia; Łojkowska, Anna; Żaczek, Anna J.; Lokhorst, Henk; van de Donk, Niels W.C.J.; Nijhof, Inger; Prins, Henk Jan; Zijlstra, Josée M.; Idema, Sander; Baayen, Johannes C.; Teunissen, Charlotte E.; Killestein, Joep; Besselink, Marc G.; Brammen, Lindsay; Bachleitner-Hofmann, Thomas; Mateen, Farrah; Plukker, John T.M.; Heger, Michal; de Mast, Quirijn; Lisman, Ton; Pegtel, D. Michiel; Bogaard, Harm Jan; Jassem, Jacek; Supernat, Anna; Mehra, Niven; Gerritsen, Winald; de Kroon, Cornelis D.; Lok, Christianne A.R.; Piek, Jurgen M.J.; Steeghs, Neeltje; van Houdt, Winan J.; Brakenhoff, Ruud H.; Sonke, Gabe S.; Verheul, Henk M.; Giovannetti, Elisa; Kazemier, Geert; Sabrkhany, Siamack; Schuuring, Ed; Sistermans, Erik A.; Wolthuis, Rob; Meijers-Heijboer, Hanne; Dorsman, Josephine; Oudejans, Cees; Ylstra, Bauke; Westerman, Bart A.; van den Broek, Daan; Koppers-Lalic, Danijela; Wesseling, Pieter; Nilsson, R. Jonas A.; Vandertop, W. Peter; Noske, David P.; Tannous, Bakhos A.; Sol, Nik; Best, Myron G.; Wurdinger, Thomas
(2022) Cancer Cell, volume 40, issue 9, pp. 999 - 1009.e6
(Article)
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
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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.
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Keywords: blood, blood platelets, cancer, early detection, liquid biopsy, RNA, TEP, Oncology, Cancer Research
ISSN: 1535-6108
Publisher: Cell Press
Note: Funding Information: 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. Funding Information: 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. Publisher Copyright: © 2022 The Author(s)
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