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Molecular Diagnostics

Toward platelet transcriptomics in cancer diagnosis, prognosis and therapy

Abstract

Widespread adoption of next-generation techniques such as RNA-sequencing (RNA-seq) has enabled research examining the transcriptome of anucleate blood platelets in health and disease, thus revealing a rich platelet transcriptomic signature that is reprogrammed in response to disease. Platelet signatures not only capture information from parent megakaryocytes and progenitor hematopoietic stem cells but also the bone marrow microenvironment, and underlying disease states. In cancer, the substantive body of research in patients with solid tumours has identified distinct signatures in ‘tumour-educated platelets’, reflecting influences of the tumour, stroma and vasculature on splicing, sequestration of tumour-derived RNAs, and potentially cytokine and microvesicle influences on megakaryocytes. More recently, platelet RNA expression has emerged as a highly sensitive approach to profiling chronic progressive haematologic malignancies, where the combination of large data cohorts and machine-learning algorithms enables precise feature selection and potential prognostication. Despite these advances, however, our ability to translate platelet transcriptomics toward clinical diagnostic and prognostic efforts remains limited. In this Perspective, we present a few actionable steps for our basic, translational and clinical research communities in advancing the utility of the platelet transcriptome as a highly sensitive biomarker in cancer and collectively enable efforts toward clinical translation and patient benefit.

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Acknowledgements

AK extends special thanks to mentors at Stanford University, in particular, Prof. Jason Gotlib (Stanford MPN Translational Research Center, and the Stanford Cancer Institute, Stanford University School of Medicine) and the patients at the Stanford Cancer Center for their generous participation in MPN platelet transcriptomic research.

Funding

This work was funded by US National Institutes of Health Grants 1K08HG010061-01A1 and 3UL1TR001085-04S1 to AK and the UK National Institute for Health Research to ST.

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AK and ST conceived the article and wrote the first draft. AK and ST researched the literature for the article. AK completed the subsequent versions and resubmission as ST had to be away on personal leave.

Corresponding author

Correspondence to Anandi Krishnan.

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The authors declare no competing interests.

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Krishnan, A., Thomas, S. Toward platelet transcriptomics in cancer diagnosis, prognosis and therapy. Br J Cancer (2021). https://doi.org/10.1038/s41416-021-01627-z

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