TY - JOUR
T1 - Tumor-Educated Platelet RNA for the Detection and (Pseudo)progression Monitoring of Glioblastoma
AU - Sol, Nik
AU - 't Veld, Sjors G. J. G. in
AU - Vancura, Adrienne
AU - Tjerkstra, Maud
AU - Leurs, Cyra
AU - Rustenburg, Francois
AU - Schellen, Pepijn
AU - Verschueren, Heleen
AU - Post, Edward
AU - Zwaan, Kenn
AU - Ramaker, Jip
AU - Wedekind, Laurine E.
AU - Tannous, Jihane
AU - Ylstra, Bauke
AU - Killestein, Joep
AU - Mateen, Farrah
AU - Idema, Sander
AU - Hamer, Philip C. de Witt
AU - Navis, Anna C.
AU - Leenders, William P. J.
AU - Hoeben, Ann
AU - Moraal, Bastiaan
AU - Noske, David P.
AU - Vandertop, W. Peter
AU - Nilsson, R. Jonas A.
AU - Tannous, Bakhos A.
AU - Wesseling, Pieter
AU - Reijneveld, Jaap C.
AU - Best, Myron G.
AU - Wurdinger, Thomas
N1 - Funding Information:
Financial support was provided by European Research Council E8626 (to R.J.A.N. and T.W.) and 336540 and 713727 (to T.W.), Dutch Organisation of Scientific Research 93612003 and 91711366 (to T.W.), the Dutch Cancer Society (to T.W. and J.C.R.), Stichting STOPhersentumoren.nl (to N.S. P.W. J.C.R. M.G.B. and T.W.), NIH/NCI CA176359 and CA069246 (to B.A.T.), CFF Norrland (to R.J.A.N.), and the Swedish Research Council (to R.J.A.N.). We are thankful to Dirk van Essen, Paul Eijk, Reno Bladergroen, Mirte Muller, Jillian Bracht, Michelle Esenkbrink, Leon Wils, Francesca Favaro, Jilian D. Schoonhoven, Michal Hegar, Saskia C. de Jager, Rolf T. Urbanus, Imo E. Hoefer, Gerard Pasterkamp, Daan van den Broek, Adrianus J. de Langen, Egbert F. Smit, Michel M. van den Heuvel, M.C.M. Kouwenhoven, and Henk M. Verheul for support and Sebastiaan van de Sand (SIT B.V.) for computational resources. N.S. M.G.B. J.C.R. and T.W. designed the study and wrote the manuscript. N.S. M.T. C.L. J.T. B.Y. J.K. F.M. S.I. A.C.N. W.P.J.L. A.H. B.M. D.P.N. W.P.V. R.J.A.N. B.A.T. P.W. and J.C.R. provided clinical samples and data. N.S. A.V. F.R. P.S. H.V. E.P. L.E.W. J.T. M.G.B. and T.W. performed sample processing for RNA-seq. N.S. S.G.J.G.i.t.V. A.V. P.W. B.A.T. M.G.B. and T.W. performed data analyses and interpretation. All authors provided critical comments on the manuscript. M.G.B. R.J.A.N. and T.W. are inventors on relevant patent applications. T.W. and R.J.A.N. received funding from Illumina and are shareholders of GRAIL, Inc.
Funding Information:
M.G.B., R.J.A.N., and T.W. are inventors on relevant patent applications. T.W. and R.J.A.N. received funding from Illumina and are shareholders of GRAIL, Inc.
Funding Information:
Financial support was provided by European Research Council E8626 (to R.J.A.N. and T.W.) and 336540 and 713727 (to T.W.), Dutch Organisation of Scientific Research 93612003 and 91711366 (to T.W.), the Dutch Cancer Society (to T.W. and J.C.R.), Stichting STOPhersentumoren.nl (to N.S., P.W., J.C.R., M.G.B., and T.W.), NIH/NCI CA176359 and CA069246 (to B.A.T.), CFF Norrland (to R.J.A.N.), and the Swedish Research Council (to R.J.A.N.). We are thankful to Dirk van Essen, Paul Eijk, Reno Bladergroen, Mirte Muller, Jillian Bracht, Michelle Esenkbrink, Leon Wils, Francesca Favaro, Jilian D. Schoonhoven, Michal Hegar, Saskia C. de Jager, Rolf T. Urbanus, Imo E. Hoefer, Gerard Pasterkamp, Daan van den Broek, Adrianus J. de Langen, Egbert F. Smit, Michel M. van den Heuvel, M.C.M. Kouwenhoven, and Henk M. Verheul for support and Sebastiaan van de Sand (SIT B.V.) for computational resources.
Publisher Copyright:
© 2020 The Authors
PY - 2020/10/20
Y1 - 2020/10/20
N2 - Tumor-educated platelets (TEPs) are potential biomarkers for cancer diagnostics. We employ TEP-derived RNA panels, determined by swarm intelligence, to detect and monitor glioblastoma. We assessed specificity by comparing the spliced RNA profile of TEPs from glioblastoma patients with multiple sclerosis and brain metastasis patients (validation series, n = 157; accuracy, 80%; AUC, 0.81 [95% CI, 0.74-0.89; p < 0.001]). Second, analysis of patients with glioblastoma versus asymptomatic healthy controls in an independent validation series (n = 347) provided a detection accuracy of 95% and AUC of 0.97 (95% CI, 0.95-0.99; p < 0.001). Finally, we developed the digitalSWARM algorithm to improve monitoring of glioblastoma progression and demonstrate that the TEP tumor scores of individual glioblastoma patients represent tumor behavior and could be used to distinguish false positive progression from true progression (validation series, n = 20; accuracy, 85%; AUC, 0.86 [95% CI, 0.70-1.00; p < 0.012]). In conclusion, TEPs have potential as a minimally invasive biosource for blood-based diagnostics and monitoring of glioblastoma patients.
AB - Tumor-educated platelets (TEPs) are potential biomarkers for cancer diagnostics. We employ TEP-derived RNA panels, determined by swarm intelligence, to detect and monitor glioblastoma. We assessed specificity by comparing the spliced RNA profile of TEPs from glioblastoma patients with multiple sclerosis and brain metastasis patients (validation series, n = 157; accuracy, 80%; AUC, 0.81 [95% CI, 0.74-0.89; p < 0.001]). Second, analysis of patients with glioblastoma versus asymptomatic healthy controls in an independent validation series (n = 347) provided a detection accuracy of 95% and AUC of 0.97 (95% CI, 0.95-0.99; p < 0.001). Finally, we developed the digitalSWARM algorithm to improve monitoring of glioblastoma progression and demonstrate that the TEP tumor scores of individual glioblastoma patients represent tumor behavior and could be used to distinguish false positive progression from true progression (validation series, n = 20; accuracy, 85%; AUC, 0.86 [95% CI, 0.70-1.00; p < 0.012]). In conclusion, TEPs have potential as a minimally invasive biosource for blood-based diagnostics and monitoring of glioblastoma patients.
KW - RESPONSE ASSESSMENT
KW - MESSENGER-RNA
KW - ADJUVANT TEMOZOLOMIDE
KW - BLOOD-PLATELETS
KW - EANO GUIDELINE
KW - POOR SURVIVAL
KW - CANCER
KW - NEUROONCOLOGY
KW - CELLS
KW - LUNG
U2 - 10.1016/j.xcrm.2020.100101
DO - 10.1016/j.xcrm.2020.100101
M3 - Article
C2 - 33103128
SN - 2666-3791
VL - 1
JO - Cell Reports Medicine
JF - Cell Reports Medicine
IS - 7
M1 - 100101
ER -