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 - 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)
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.
KW - RNA
KW - TEP
KW - blood
KW - blood platelets
KW - cancer
KW - early detection
KW - liquid biopsy
UR - https://www.scopus.com/pages/publications/85137385164
UR - https://www.ncbi.nlm.nih.gov/pubmed/36055228
UR - https://www.scopus.com/pages/publications/85137385164
U2 - 10.1016/j.ccell.2022.08.006
DO - 10.1016/j.ccell.2022.08.006
M3 - Article
C2 - 36055228
SN - 1535-6108
VL - 40
SP - 999-1009.e6
JO - Cancer cell
JF - Cancer cell
IS - 9
ER -
SDG 3 Good Health and Well-being