Proteomics

Dataset Information

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Omics Analysis of Pancreatic Cancer Platelets Reveals Active “Education”, including Dysregulation of Splicing Signature and Inhibition of SPARC by Modified Forms of miRNAs


ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is associated with hypercoagulation, but molecular mechanisms underlying PDAC/platelets interaction remain controversial. PDAC cells can activate platelets and change their RNA and protein content, thus, we performed an integrative study investigating the biological processes of differentially spliced mRNAs and expressed miRNAs, as well as proteins. To focus on these “dangerous liaisons”, we used benign disease as a background noise correction for putative inflammatory signals. Gene set enrichment analysis on differential miRNAs, RNA transcripts and proteins revealed an enrichment of RNA splicing, mRNA processing and translation initiation on miRNAs and proteins and depletion on RNA transcripts, as previously described. Moreover, correlation analyses revealed a specific regulation on SPARC RNA transcripts by isomiRs involved in cancer signaling, suggesting a specific modulation/”education” in PDAC platelets. We identified HBA1, HBD, CA1 and AGT as protein markers in PDAC platelets. In conclusion, our data show that platelets change their biological repertoire in the presence of PDAC, through dysregulation of miRNAs and splicing factors, supporting the presence of a clear de novo protein machinery that can “educate” the platelet.

INSTRUMENT(S): Q Exactive HF, Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Platelet, Platelet

DISEASE(S): Pancreatic Ductal Adenocarcinoma

SUBMITTER: Sander Piersma  

LAB HEAD: Connie Ramona Jimenez

PROVIDER: PXD022514 | Pride | 2021-09-09

REPOSITORIES: Pride

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Publications


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  ...[more]

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