Extracellular vesicles proteins for early cancer diagnosis: From omics to biomarkers

Extracellular vesicles (EVs) are a promising source of early biomarkers for cancer diagnosis. They are enriched with diverse molecular content, such as proteins, DNA, mRNA, miRNA, lipids, and metabolites. EV proteins have been widely investigated as potential biomarkers since they reflect specific patient conditions. However, although many markers have been validated and confirmed using external cohorts of patients and different analytical approaches, no EV protein markers are approved for diagnostic use. This review presents the primary strategies adopted using mass spectrometry and immune-based techniques to identify and validate EV protein biomarkers. We report and discuss recent scientific research focusing on cancer biomarker discovery through EVs, emphasizing their significant potential for the tempestive diagnosis of several cancer typologies. Finally, recent advancements in the standardization of EV isolation and quantitation through the development of easy-to-use and high-throughput kits for sample preparation-that should make protein EV biomarkers more reliable and accessible-are presented. The data reported here showed that there are still several challenges to be addressed before a protein vesicle marker becomes an essential tool in diagnosing cancer.