Omics Analysis of Educated Platelets in Cancer and Benign Disease of the Pancreas

Pancreatic ductal adenocarcinoma (PDAC) is traditionally associated with thrombocytosis/hypercoagulation and novel insights on platelet-PDAC "dangerous liaisons" are warranted. Here we performed an integrative omics study investigating the biological processes of mRNAs and expressed miRNAs...

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Bibliographic Details
Published in:Cancers 2020-12, Vol.13 (1), p.66
Main Authors: Mantini, Giulia, Meijer, Laura L, Glogovitis, Ilias, In 't Veld, Sjors G J G, Paleckyte, Rosita, Capula, Mjriam, Le Large, Tessa Y S, Morelli, Luca, Pham, Thang V, Piersma, Sander R, Frampton, Adam E, Jimenez, Connie R, Kazemier, Geert, Koppers-Lalic, Danijela, Wurdinger, Thomas, Giovannetti, Elisa
Format: Article
Language:English
Subjects:
Adenocarcinoma
Age
Benign
Biomarkers
Blood platelets
Cancer
Disease
Gene regulation
Genes
Inflammation
Investigations
mRNA processing
Nucleotides
Osteonectin
Pancreas
Platelets
Protein expression
Protein synthesis
Proteins
Proteomics
RNA polymerase
RNA processing
Splicing factors
Thrombocytosis
Transcription
Translation initiation
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Summary:Pancreatic ductal adenocarcinoma (PDAC) is traditionally associated with thrombocytosis/hypercoagulation and novel insights on platelet-PDAC "dangerous liaisons" are warranted. Here we performed an integrative omics study investigating the biological processes of mRNAs and expressed miRNAs, as well as proteins in PDAC blood platelets, using benign disease as a reference for inflammatory noise. Gene ontology mining revealed enrichment of RNA splicing, mRNA processing and translation initiation in miRNAs and proteins but depletion in RNA transcripts. Remarkably, correlation analyses revealed a negative regulation on SPARC transcription by isomiRs involved in cancer signaling, suggesting a specific "education" in PDAC platelets. Platelets of benign patients were enriched for non-templated additions of G nucleotides (#ntaG) miRNAs, while PDAC presented length variation on 3' (lv3p) as the most frequent modification on miRNAs. Additionally, we provided an actionable repertoire of PDAC and benign platelet-ome to be exploited for future studies. In conclusion, our data show that platelets change their biological repertoire in patients with PDAC, through dysregulation of miRNAs and splicing factors, supporting the presence of protein machinery that can "educate" the platelet. These novel findings could be further exploited for innovative liquid biopsies platforms as well as possible therapeutic targets.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13010066