RNA-Seq of Tumor-Educated Platelets Enables Blood-Based Pan-Cancer, Multiclass, and Molecular Pathway Cancer Diagnostics

Abstract

SummaryTumor-educated blood platelets (TEPs) are implicated as central players in the systemic and local responses to tumor growth, thereby altering their RNA profile. We determined the diagnostic potential of TEPs by mRNA sequencing of 283 platelet samples. We distinguished 228 patients with localized and metastasized tumors from 55 healthy individuals with 96% accuracy. Across six different tumor types, the location of the primary tumor was correctly identified with 71% accuracy. Also, MET or HER2-positive, and mutant KRAS, EGFR, or PIK3CA tumors were accurately distinguished using surrogate TEP mRNA profiles. Our results indicate that blood platelets provide a valuable platform for pan-cancer, multiclass cancer, and companion diagnostics, possibly enabling clinical advances in blood-based “liquid biopsies”.

The Novel Association of Circulating Tumor Cells and Circulating Megakaryocytes with Prostate Cancer Prognosis

“…This is consistent to the finding of CD34 expression in mature-appearing megakaryocytes in reactive and disorders of bone marrows (40), and increased ploidization of megakaryocytes has been reported in patients with metastatic tumors (43). Platelets, which are released from megakaryocytes in bone marrow, have recently been recognized to play an important role in cancer metastasis (44,45), and the gene expression profile of platelets has been shown to efficiently distinguish individuals with or without cancers (46). Platelet counts have also been investigated for cancer prognosis, and the data are still in conflict (47).…”

DNA-Guided Precision Medicine for Cancer: A Case of Irrational Exuberance?

“…One additional limitation of RNA-based diagnostics appears to be that, unlike DNA, cell-free tumor RNA cannot be analyzed from the blood of tumor-bearing patients. However, a recent study suggests that blood platelets accumulate RNA molecules from cancer cells, enabling transcriptomic analyses for diagnostic purposes potentially using as little as a single drop of patient blood (30). Such technologies, when further validated, may be valuable to further elucidate the interplay between gene expression and oncogenic driver mutations in cancer.…”

Report from the II Melanoma Translational Meeting of the Spanish Melanoma Group (GEM)

“…This interaction affects the expression of relevant genes in tumor cells, but also alters the RNA profile of blood platelets (24,25). Cancer cells and the tumor microenvironment release signals that ultimately activate platelet surface receptors, induce specific splicing of pre-mRNAs in circulating platelets, and transform normal platelets to tumor educated platelets (TEP) (26). The combination of these splicing events, as well as the capacity of platelets to ingest circulating mRNA, provides TEPs with a dynamic RNA repertoire that can be used for cancer diagnostics.…”

“…In addition, plateletderived RNA can be used for the real-time monitoring of ALK rearranged NSCLC patients treated with specific ALK inhibitors (31). Also, Thomas Wurdinger's group has demonstrated that TEPs can be successfully used for the detection of cancer among healthy individuals, and for identifying both the location of the primary tumor, as well as the genetic driver alteration among cancer patients (26). Specifically, they found that sequencing the mRNA from TEPs, distinguishes cancer patients from healthy individuals with 96% accuracy.…”