Blood-Based Circulating RNAs as Preventive, Diagnostic, Prognostic and Druggable Biomarkers for Pancreatic Ductal Adenocarcinoma

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive disease with a poor prognosis. So far, serum CA19–9 (carbohydrate antigen 19–9) is the only blood biomarker that is routinely used in clinical practice. Recent studies have uncovered a stable presence of circulating RNAs in blood, which are studied and developed into preventive/predictive, diagnostic, prognostic and druggable biomarkers for PDAC. Blood RNAs consist of two major categories: mRNAs (messenger RNAs) and ncRNAs (noncoding RNAs); both of them exist either in a cell-free or in a cellular form. Due to the abundance of RNases in blood, cell-free mRNA poses only a limited clinical significance. Taking advantage of next-generation sequencing techniques, mRNA profiles of CTCs (circulating tumour cells) or TEPs (tumour-educated platelets) were shown to be promising diagnostic biomarkers for PDAC. As for ncRNAs, blood miRNA (microRNA) is presently the most characterized one. The alteration in blood miRNAs tends to take place late in the disease course of PDAC, arguing against its role as a preventive or predictive biomarker for early detection. Despite a lower specificity, blood miRNAs as diagnostic biomarkers are generally as useful as serum CA19–9. However, their measurement is still not as easy and standardized as serum CA19–9, which prevents their use in daily clinical practice. Meanwhile, many diagnostic blood miRNAs are also prognostic biomarkers that can be used for patient stratification. Finally, a few blood miRNAs are currently explored as druggable biomarkers at the preclinical stage.