Extracellular Vesicles as Potential Biomarkers for Early Detection and Diagnosis of Pancreatic Cancer

Abstract

Pancreatic carcinoma (PC) is highly metastatic, and it tends to be detected at advanced stages. Identifying and developing biomarkers for early detection of PC is crucial for a potentially curative treatment. Extracellular vesicles (EVs) are bilayer lipid membrane-structured nanovesicles found in various human bodily fluids, and they play important roles in tumor biogenesis and metastasis. Cancer-derived EVs are enriched with DNA, RNA, protein, and lipid, and they have emerged as attractive diagnostic biomarkers for early detection of PC. In this article, we provided an overview of the cell biology of EVs and their isolation and analysis, and their roles in cancer pathogenesis and progression. Multiplatform analyses of plasma-based exosomes for genomic DNA, micro RNA, mRNA, circular RNA, and protein for diagnosis of PC were critically reviewed. Numerous lines of evidence demonstrate that liquid biopsy with analysis of EV-based biomarkers has variable performance for diagnosis of PC. Future investigation is indicated to optimize the methodology for isolating and analyzing EVs and to identify the combination of EV-based biomarkers and other clinical datasets, with the goal of improving the predictive value, sensitivity, and specificity of screening tests for early detection and diagnosis of PC.

Keywords: early detection; exosomes; extracellular vesicles; liquid biopsy; pancreatic carcinoma.

Figure 1

Roles of EVs in intercellular communication between tumor cells and stromal cells in local and distant microenvironments, leading to tumor metastasis, progression, and resistance to treatment.

Figure 2

Integrative analysis of circulating EV-derived biomarkers with other datasets using machine learning-based algorithms for detection of pancreatic cancer (PC) in asymptomatic individuals, detection of PC at early stage, and distinguishing PC from other types of cancer.