Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Cancers, 2020-05, Vol.12 (6), p.1372

Ort / Verlag

Switzerland: MDPI

Erscheinungsjahr

2020

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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.