Exosomal ephrinA2 derived from serum as a potential biomarker for prostate cancer

Abstract

Up-regulation of serum ephrinA2 is common in various malignancies and has been suggested as a potential biomarker for the diagnosis and prognosis of prostate cancer (PCa). However, the type of serum ephrinA2 expressed in PCa patients remains elusive. Furthermore, the level of exosomal ephrinA2 derived from serum is increased in patients with osteoporosis, a common complication of PCa patients undergoing androgen deprivation therapy. It is unknown whether exosomes derived from PCa patient serum contains ephrinA2. In this study, we explored the ephrinA2 expression in whole serum and tissues and identified the circulating exosomal ephrinA2 as a potential biomarker for PCa. Exosomes were isolated from patient sera by differential centrifugation and the presence of ephrinA2 was confirmed via electron microscopy and western blotting. The type of ephrinA2 in serum was evaluated by western blotting. The expression of serum ephrinA2 including secreted and cleaved ephrinA2 and exosomal ephrinA2 were detected by ELISA and western blotting. Compared with benign prostatic hyperplasia (BPH) and controls, the levels of whole serum ephrinA2 and exosomal ephrinA2 were significantly higher in PCa patients. Moreover, exosomal ephrinA2 expression was positively correlated with TNM staging and Gleason score of PCa patients. The diagnostic efficiency of exosomal ephrinA2 was superior to that of whole serum ephrinA2 and serum PSA in distinguishing PCa patients from those from BPH patents. Our study indicates that exosomal ephrinA2 has high potential as a biomarker for the presence of PCa and offers a new therapeutic target for this disease.

Diagnostic performance of circulating exosomes in human cancer: A meta‐analysis

“…After detailed evaluation of the full texts, 85 articles were excluded for the following reasons: (a) 34 studies not for diagnostic research; (b) 34 studies with insufficient data; (c) 7 studies based on combined diagnosis; (d) 1 study with no difference in expression; (e) 6 studies with sample size less than 20 in either case or control group; and (f) 3 studies with non‐English full‐text. Finally, a total of 70 studies from 42 publications 15‐56 involving 3161 cases and 2763 controls were analyzed in the meta‐analysis.…”

“…All cancer cases were confirmed pathologically. There were fifteen cancer types: lung cancer (LC, n = 7), [15][16][17][18][19][20][21] esophageal cancer (EC, n = 1), 22 gastric cancer (GC, n = 5), [23][24][25][26][27] colorectal cancer (CRC, n = 5), [28][29][30][31][32] hepatocellular carcinoma (HCC, n = 4), [33][34][35][36] pancreatic cancer (PC, n = 3), [37][38][39] ovarian cancer (OC, n = 3), [40][41][42] glioma (n = 3), [43][44][45] clear cell renal cell carcinoma (ccRCC, n = 2), 50,51 bladder cancer (BC, n = 3), 46,48,49 prostate cancer (PCa, n = 2), 47,52 osteosarcoma (n = 1), 53 multiple myeloma (MM, n = 1), 54 melanoma (n = 1), 55 and laryngeal squamous cell carcinoma (LSCC, n = 1). 56 Publication years of all included researches range from 2013 to 2019.…”

Changes in phospholipid metabolism in exosomes of hormone-sensitive and hormone-resistant prostate cancer cells

“…The next step would be to confirm that our method works for isolating exosomes from serum, urine and other secretions 52 . Our modified PEG method may need further refinement, such as through incorporation of an ultracentrifugation step, since transmission electron microscopy revealed that a small proportion of our exosomes had diameters >200 nm.…”

Isolation and characterization of extracellular vesicles for clinical applications in cancer – time for standardization?

“…136 Ascites derived EV associated E-cadherin has diagnostic utility in ovarian cancer and serum EV associated EphrinA2 may aid diagnosis of prostate cancer. 137,138 There is a large number of research studies published regarding the analysis of EVs as biomarkers for cancer. To assess the EV isolation and characterization methods employed by the large number of EV studies, we selected studies based on a previous meta-analysis study that looked at the clinical signicance of EVs in cancer.…”