Circulating platelets as liquid biopsy sources for cancer detection

Nucleic acids and proteins are shed into the bloodstream by tumor cells and can be exploited as biomarkers for the detection of cancer. In addition, cancer detection biomarkers can also be nontumor-derived, having their origin in other organs and cell types. Hence, liquid biopsies provide a source of direct tumor cell-derived biomolecules and indirect nontumor-derived surrogate markers that circulate in body fluids or are taken up by circulating peripheral blood cells. The capacity of platelets to take up proteins and nucleic acids and alter their megakaryocyte-derived transcripts and proteins in response to external signals makes them one of the richest liquid biopsy biosources. Platelets are the second most abundant cell type in peripheral blood and are routinely isolated through well-established and fast methods in clinical diagnostics but their value as a source of cancer biomarkers is relatively recent. Platelets do not have a nucleus but have a functional spliceosome and protein translation machinery, to process RNA transcripts. Platelets emerge as important repositories of potential cancer biomarkers, including several types of RNAs (mRNA, miRNA, circRNA, lncRNA, and mitochondrial RNA) and proteins, and several preclinical studies have highlighted their potential as a liquid biopsy source for detecting various types and stages of cancer. Here, we address the usability of platelets as a liquid biopsy for the detection of cancer. We describe several studies that support the use of platelet biomarkers in cancer diagnostics and discuss what is still lacking for their implementation into the clinic.