Detection and localization of early- and late-stage cancers using platelet RNA
Sjors G. J. G. In ‘t Veld, Mohammad Arkani, Edward P. 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, J. 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, Romée Harting, Annemijn Gregory, Markus 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 Lewandrowski, Philip C. De Witt Hamer, Mathilde C.M. 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.A. de Jager, Adriaan O. Kraaijeveld, Gerard Pasterkamp, Minke Smits, Jack A. Schalken, Sylwia Łapińska‐Szumczyk, Anna Łojkowska, Anna J. Żaczek, Henk M. Lokhorst, Niels W.C.J. van de Donk, Inger S. 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 J. Mateen, John Th. M. Plukker, Michal Heger, Quirijn de Mast, Ton Lisman, D. Michiel Pegtel, Harm Jan Bogaard, Jacek Jassem, Anna Supernat, Niven Mehra, Winald R. Gerritsen, Cor D. de Kroon, Christianne Lok, Jurgen M.J. Piek, Neeltje Steeghs, Winan J. van Houdt, Ruud H. Brakenhoff, Gabe S. Sonke, Henk M.W. Verheul, Elisa Giovannetti, Geert Kazemier, Siamack Sabrkhany, Ed Schuuring, Erik A. Sistermans
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.