Abstract

Blood-based ‘liquid biopsies’ provide a means for minimally invasive molecular diagnostics, overcoming limitations of tissue acquisition. Early detection of cancer, clinical cancer diagnostics, and companion diagnostics are regarded as important applications of liquid biopsies. It has been reported that tumor-educated platelets (TEPs) may enable blood-based cancer diagnostics. Platelets have emerged as central players in the systemic and local responses to tumor growth. Confrontation of platelets with tumor cells via transfer of tumor-associated biomolecules (‘education’) is an emerging concept and can result in the sequestration of biomolecules. Moreover, external stimuli induce specific splicing of pre-mRNAs in circulating platelets. Platelets are considered to undergo queue-specific splice events in response to signals released by cancer cells and the tumor microenvironment - such as stromal and immune cells. The combination of specific splice events in response to external signals and the capacity of platelets to directly ingest (spliced) circulating mRNA can provide TEPs with a highly dynamic mRNA repertoire, with potential applicability to cancer diagnostics. We determined the diagnostic potential of TEPs by mRNA sequencing of platelet samples. Blood platelet samples of >1000 patients with cancer covering multiple tumor types and healthy donors were analyzed. Healthy donors, pan-cancer, and individual cancer classes were distinguished by a self-learning support vector machine (SVM) algorithm, using a set of spliced transcripts with moderate to high expression. These results indicate that blood platelets provide a valuable platform for pan-cancer, multiclass cancer diagnostics, possibly enabling clinical advances in blood-based ‘liquid biopsies’.