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. 2022 Sep 12;40(9):999-1009.e6.
doi: 10.1016/j.ccell.2022.08.006. Epub 2022 Sep 1.

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

Sjors G J G In 't Veld  1 , Mohammad Arkani  2 , Edward Post  3 , Mafalda Antunes-Ferreira  3 , Silvia D'Ambrosi  3 , Daan C L Vessies  4 , Lisa Vermunt  5 , Adrienne Vancura  3 , Mirte Muller  6 , Anna-Larissa N Niemeijer  7 , Jihane Tannous  8 , Laura L Meijer  9 , Tessa Y S Le Large  9 , Giulia Mantini  10 , Niels E Wondergem  11 , Kimberley M Heinhuis  12 , Sandra van Wilpe  13 , A Josien Smits  7 , Esther E E Drees  14 , Eva Roos  15 , Cyra E Leurs  16 , Lee-Ann Tjon Kon Fat  17 , Ewoud J van der Lelij  3 , Govert Dwarshuis  3 , Maarten J Kamphuis  3 , Lisanne E Visser  3 , Romee Harting  3 , Annemijn Gregory  3 , Markus W Schweiger  18 , Laurine E Wedekind  3 , Jip Ramaker  3 , Kenn Zwaan  3 , Heleen Verschueren  3 , Idris Bahce  7 , Adrianus J de Langen  6 , Egbert F Smit  6 , Michel M van den Heuvel  19 , Koen J Hartemink  20 , Marijke J E Kuijpers  21 , Mirjam G A Oude Egbrink  22 , Arjan W Griffioen  10 , Rafael Rossel  23 , T Jeroen N Hiltermann  24 , Elizabeth Lee-Lewandrowski  25 , Kent B Lewandrowski  25 , Philip C De Witt Hamer  3 , Mathilde Kouwenhoven  26 , Jaap C Reijneveld  27 , William P J Leenders  28 , Ann Hoeben  29 , Irma M Verdonck-de Leeuw  30 , C René Leemans  31 , Robert J Baatenburg de Jong  32 , Chris H J Terhaard  33 , Robert P Takes  34 , Johannes A Langendijk  35 , Saskia C de Jager  36 , Adriaan O Kraaijeveld  37 , Gerard Pasterkamp  36 , Minke Smits  13 , Jack A Schalken  38 , Sylwia Łapińska-Szumczyk  39 , Anna Łojkowska  39 , Anna J Żaczek  40 , Henk Lokhorst  41 , Niels W C J van de Donk  41 , Inger Nijhof  41 , Henk-Jan Prins  41 , Josée M Zijlstra  41 , Sander Idema  3 , Johannes C Baayen  3 , Charlotte E Teunissen  5 , Joep Killestein  16 , Marc G Besselink  15 , Lindsay Brammen  42 , Thomas Bachleitner-Hofmann  43 , Farrah Mateen  44 , John T M Plukker  45 , Michal Heger  46 , Quirijn de Mast  47 , Ton Lisman  48 , D Michiel Pegtel  14 , Harm-Jan Bogaard  7 , Jacek Jassem  49 , Anna Supernat  40 , Niven Mehra  13 , Winald Gerritsen  13 , Cornelis D de Kroon  50 , Christianne A R Lok  51 , Jurgen M J Piek  52 , Neeltje Steeghs  12 , Winan J van Houdt  53 , Ruud H Brakenhoff  11 , Gabe S Sonke  54 , Henk M Verheul  13 , Elisa Giovannetti  55 , Geert Kazemier  9 , Siamack Sabrkhany  56 , Ed Schuuring  57 , Erik A Sistermans  58 , Rob Wolthuis  59 , Hanne Meijers-Heijboer  59 , Josephine Dorsman  59 , Cees Oudejans  60 , Bauke Ylstra  14 , Bart A Westerman  3 , Daan van den Broek  4 , Danijela Koppers-Lalic  3 , Pieter Wesseling  61 , R Jonas A Nilsson  17 , W Peter Vandertop  3 , David P Noske  3 , Bakhos A Tannous  8 , Nik Sol  26 , Myron G Best  62 , Thomas Wurdinger  63
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Free article

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

Sjors G J G In 't Veld et al. Cancer Cell. .
Free 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 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.

Keywords: RNA; TEP; blood; blood platelets; cancer; early detection; liquid biopsy.

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Conflict of interest statement

Declaration of interests 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.

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