CD63-positive extracellular vesicles are potential diagnostic biomarkers of pancreatic ductal adenocarcinoma

• Published in: BMC gastroenterology 2022-03, Vol.22 (1), p.153-153, Article 153
• Main Authors: Odaka, Haruki, Hiemori, Keiko, Shimoda, Asako, Akiyoshi, Kazunari, Tateno, Hiroaki
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Adenocarcinoma - diagnosis; Alzheimer's disease; Biological markers; Biomarker; Biomarkers; Biomarkers, Tumor; Cancer; Case-Control Studies; CD63; CD63 antigen; Cloning; Correlation analysis; Diagnosis; Enzyme-linked immunosorbent assay; Exosome; Extracellular vesicle; Extracellular vesicles; Extracellular Vesicles - pathology; Gastroenterology; Health aspects; Heparan sulfate; Hospitals; Humans; Medical prognosis; Morphology; Nanoparticles; Pancreas; Pancreatic cancer; Pancreatic ductal adenocarcinoma; Pancreatic Neoplasms - pathology; Pathology; Patients; Phosphatidylserine; Platelet; Platelets; Prognosis; Serum levels; Tetraspanin 30; Tumors
• ISSN: 1471-230X; 1471-230X
• DOI: 10.1186/s12876-022-02228-7

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest gastrointestinal cancers with a 5-year survival rate of less than 10%. Biomarkers for early PDAC detection are useful in treating patients with PDAC. Extracellular vesicles (EVs) are lipid-bound vesicles that are potential biomarkers of various diseases such as PDAC. In this study, we quantitatively measured the serum levels of EVs (CD63 -EVs) or platelet-derived EVs (CD41 - and CD61 -EVs) and evaluated their potential use as biomarkers of PDAC. We measured the serum levels of CD63 -, CD41 -, CD61 -EVs using sandwich enzyme-linked immunosorbent assay based on Tim4 with specificity for phosphatidylserine on EVs in age- and sex-matched healthy controls (HCs, n = 39) and patients with PDAC (n = 39). We also examined the effect of tumor burden on the serum EV levels after surgical resection (n = 28). CA19-9, a clinical PDAC biomarker, was also measured for comparison. Serum levels of CD63 -EVs, CD41 -EVs, and CD61 -EVs were significantly increased in patients with PDAC compared to HCs. Receiver operating characteristic analysis revealed that CD63 -EVs exhibited the highest diagnostic performance to discriminate patients with PDAC from HCs (area under the curve (AUC): 0.846), which was comparable to CA19-9 (AUC: 0.842). CA19-9 showed lower AUC values in early stages (I-II, AUC: 0.814) than in late stages (III-IV, AUC: 0.883) PDAC. Conversely, CD63 -EVs, CD41 -EVs, and CD61 -EVs showed comparable AUCs between early- and late-stage PDAC. The combined use of CA19-9 and CD63 -EVs showed a higher diagnostic performance for early-stage PDAC (AUC: 0.903) than CA19-9. The serum levels of CD63 -EVs, CD41 -EVs, CD61 -EVs, and CA19-9 decreased significantly after surgical resection, demonstrating that EVs are increased in sera of patients depending on the tumor burden. The serum levels of CD63 -EVs and platelet-derived EVs (CD41 -EVs, CD61 -EVs) are increased in patients with PDAC than HCs. Since CD63 -EVs showed a high AUC to discriminate patients with PDAC from HCs; they might be useful as potential biomarkers for PDAC.