RNA-Sequencing of Tumor-Educated Platelets, a Novel Biomarker for Blood-Based Sarcoma Diagnostics

Kimberley M Heinhuis, Sjors G J G In 't Veld, Govert Dwarshuis, Daan van den Broek, Nik Sol, Myron G Best, Frits van Coevorden, Rick L Haas, Jos H Beijnen, Winan J van Houdt, Tom Würdinger, Neeltje Steeghs

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Sarcoma is a heterogeneous group of rare malignancies arising from mesenchymal tissues. Recurrence rates are high and methods for early detection by blood-based biomarkers do not exist. Hence, development of blood-based liquid biopsies as disease recurrence monitoring biomarkers would be an important step forward. Recently, it has been shown that tumor-educated platelets (TEPs) harbor specific spliced ribonucleic acid(RNA)-profiles. These RNA-repertoires are potentially applicable for cancer diagnostics. We aim to evaluate the potential of TEPs for blood-based diagnostics of sarcoma patients. Fifty-seven sarcoma patients (active disease), 38 former sarcoma patients (cancer free for ≥3 years) and 65 healthy donors were included. RNA was isolated from platelets and sequenced. Quantified read counts were processed with self-learning particle-swarm optimization-enhanced thromboSeq analysis and subjected to analysis of variance (ANOVA) statistics. Highly correlating spliced platelet messenger RNAs (mRNAs) of sarcoma patients were compared to controls (former sarcoma + healthy donors) to identify a quantitative sarcoma-specific signature measure, the TEP-score. ANOVA analysis identified distinctive platelet RNA expression patterns of 2647 genes (false discovery rate <0.05) in sarcoma patients as compared to controls. The self-learning algorithm reached a diagnostic accuracy of 87% (validation set only; n = 53 samples, area under the curve (AUC): 0.93, 95% confidence interval (CI): 0.86-1). Our data indicates that TEP RNA-based liquid biopsies may enable for sarcoma diagnostics.

Original languageEnglish
Article number1372
JournalCancers
Volume12
Issue number6
DOIs
Publication statusPublished - Jun 2020

Keywords

  • Blood platelets
  • Liquid biopsy
  • Messenger rna
  • Sarcoma

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