P-25 A review of circulating exosomal biomarkers in the diagnosis of pancreatic cancer

Pancreatic cancer (PC) is associated with a poor prognosis, primarily due to challenges in the early diagnosis of resectable tumours. Screening at-risk patients for PC-specific circulating molecular biomarkers is potentially an optimal method of earlier detection. Currently, CA19-9 is the only clinically applied marker. However, this non-specific marker’s early PC diagnostic capabilities are insufficient. Circulating exosomes are unique as they possess numerous molecules derived from their originating cell. Thus, identification of PC-specific exosomes can lead to greater diagnostic accuracy. We conducted a systematic review of studies assessing the diagnostic efficacy of novel circulating exosomal biomarkers in pancreatic cancer patients. Following PRISMA guidelines, a comprehensive literature search yielded 875 studies across various databases (Ovid MEDLINE, Embase and Cochrane) between years 2009 and 2020. This was narrowed down to 9 studies which fulfilled the inclusion criteria. Papers were reviewed for relevant outcomes such as: primary assessment of exosomal biomarker(s) in the diagnosis of PC in human patients, reporting of diagnostic performance values (e.g., sensitivity and specificity) and analysis of tumour staging to incorporate a focus on early diagnosis. Across nine papers, there were a total of 565 participants including 331 PC patients (234 controls). Of these, four studies assessed genetic markers such as mRNA within exosomes. Four examined proteins within exosomes such as Glypican-1 (GPC1). One paper used a multianalyte panel of both exosomal proteins and genetic markers. Male to female ratio across the studies was 1.21 and the mean age was 64.1. Sensitivity, specificity, and AUC values of the exosomal biomarkers ranged from 62.5-100, 76.2-100, and 0.823-1.0, respectively. Tumour staging was reported in all studies, with 45.6% of PC patients diagnosed with early stage PC (T1-2). Exosomal biomarkers exhibited greater diagnostic performance than CA19-9 and thus warrant further validation in larger clinical trials. This can overcome contrasting findings and small sample sizes, with potential future application of these novel markers in medical practice.