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

作者：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 Nadia Niemeijer, Jihane M. Tannous, Laura L. Meijer, Tessa Y. S. Le Large, Giulia Mantini, Niels E. Wondergem, Kimberley M. Heinhuis, Sandra van Wilpe, 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, Romée Harting, Annemijn Gregory, Markus W. Schweiger, Laurine E. Wedekind, Jip Ramaker, Kenn Zwaan, Heleen Verschueren, Idris Bahce, Adrianus J. de Langen, Egbert Frederik Smit, Michel M. van den Heuvel, Koen Johan 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 C.M. Kouwenhoven, Jaap C. Reijneveld, William P. J. Leenders, Ann Hoeben, Irma M. Verdonck‐de Leeuw, Charles René Leemans, Robert J. Baatenburg de Jong, Chris H.J. Terhaard, Robert Paul Takes, Johannes Albertus Langendijk, Saskia C.A. de Jager, Adriaan O. Kraaijeveld, Gerard Pasterkamp, Minke Smits, Jack A. Schalken, Sylwia Łapińska‐Szumczyk, Anna Łojkowska, Anna Joanna Zaczek, 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 Elisabeth Teunissen, Joep Killestein, Marc G. Besselink, Lindsay Brammen, Thomas Bachleitner‐Hofmann, Farrah Jasmine Mateen, John Th. M. Plukker, Michal Heger, Quirijn de Mast, Ton Lisman, Dirk Michiel Pegtel, Harm Jan Bogaard, Jacek Jassem, Anna Maria Supernat, Niven Mehra, Winald R. Gerritsen, Cor Doede de Kroon, Christianne A. R. 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 M. D. Schuuring, Erik A. Sistermans, Rob M.F. Wolthuis, Hanne E.J. Meijers-Heijboer, Josephine C. Dorsman, Cees B.M. Oudejans, Bauke Ylstra, Bart A. Westerman, Daan van den Broek, Danijela Koppers‐Lalic, Pieter Wesseling, R. Jonas A. Nilsson, William Peter Vandertop, David P. Noske, Bakhos A. Tannous, Nik Sol, Myron G. Best, Thomas Würdinger · 发表于：Cancer Cell · 年份：2022 · DOI：10.1016/j.ccell.2022.08.006 · 被引用次数：137 · 研究领域：Cancer-related molecular mechanisms research、Cancer Genomics and Diagnostics、Extracellular vesicles in disease

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.