Researchers in a recent study published in Cancers, performed an integrative omics analysis exploring the biological processes of mRNAs, expressed miRNAs and proteins in pancreatic ductal adenocarcinoma blood platelets.
Pancreatic ductal adenocarcinoma
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy. Experts expect PDAC to become the second leading cause of cancer-related deaths by 2030. The majority of PDAC patients are diagnosed late, with disease that is typically resistant to chemotherapy. The lack of reliable biomarkers and the absence of effective therapies are the main reasons for poor survival rates. These rates range between 2 and 9%.
Recent studies have reported the use of platelets as promising sources for cancer diagnosis and early detection biomarkers. Platelets do not have a nucleus but hold a collection of megakaryocyte-derived mRNAs. They also contain a vast amount of bioactive proteins that can be secreted upon activation. These proteins can be directly synthesised by the platelets or taken up during circulation. This makes platelet profiling an appealing tool to obtain a representative picture of the status of healthy or diseased individuals. Circulating platelets are also enriched in small non-coding RNAs (ncRNAs) such as miRNAs.
Researchers have shown that platelets can alter their RNA profiles when cancer cells are present. These are referred to as tumour educated platelets (TEPs). Further investigation into the molecular mechanisms underlying this education is needed.
To further unravel the biology underlying TEP profiles in PDAC, researchers recently applied deep omics approaches including next generation sequencing for RNA and small-RNA and label-free LC-MS/MS for proteomics. They used benign pancreatic disease as the control group to elucidate the biology of platelets in patients affected by malignant tumour platelets.
The team’s results showed a high activity on RNA splicing that led to subsequent education. They also found enrichment of specific modified forms (isomiRs) of canonical miRNAs and inhibition of SPARC transcription by a specific class of isomiRs. This suggests the presence of a specific education in PDAC platelets. They also created an interactive tool to visualise expected correlations. This tool can facilitate further investigations on additional potential biomarkers and therapeutic tools.
Overall, the data shows that platelets change their biological repertoire in patients with PDAC. This occurs through dysregulation of miRNA and splicing factors, which supports the presence of de novo protein machinery that can educate platelets. The authors noted that these findings could be further exploited for innovative liquid biopsy platforms and possible therapeutic targets.
Image credit: By kjpargeter – www.freepik.com