title: Plasma-derived exosomal survivin, a plausible biomarker for early detection of prostate cancer.
abstract: BACKGROUND
  Survivin is expressed in prostate cancer (PCa), and its downregulation sensitizes PCa cells to chemotherapeutic agents in vitro and in vivo. Small membrane-bound vesicles called exosomes, secreted from the endosomal membrane compartment, contain RNA and protein that they readily transport via exosome internalization into recipient cells. Recent progress has shown that tumor-derived exosomes play multiple roles in tumor growth and metastasis and may produce these functions via immune escape, tumor invasion and angiogenesis. Furthermore, exosome analysis may provide novel biomarkers to diagnose or monitor PCa treatment.
  
  
  METHODS
  Exosomes were purified from the plasma and serum from 39 PCa patients, 20 BPH patients, 8 prostate cancer recurrent and 16 healthy controls using ultracentrifugation and their quantities and qualities were quantified and visualized from both the plasma and the purified exosomes using ELISA and Western blotting, respectively.
  
  
  RESULTS
  Survivin was significantly increased in the tumor-derived samples, compared to those from BPH and controls with virtually no difference in the quantity of Survivin detected in exosomes collected from newly diagnosed patients exhibiting low (six) or high (nine) Gleason scores. Exosome Survivin levels were also higher in patients that had relapsed on chemotherapy compared to controls.
  
  
  CONCLUSIONS
  These studies demonstrate that Survivin exists in plasma exosomes from both normal, BPH and PCa subjects. The relative amounts of exosomal Survivin in PCa plasma was significantly higher than in those with pre-inflammatory BPH and control plasma. This differential expression of exosomal Survivin was seen with both newly diagnosed and advanced PCa subjects with high or low-grade cancers. Analysis of plasma exosomal Survivin levels may offer a convenient tool for diagnosing or monitoring PCa and may, as it is elevated in low as well as high Gleason scored samples, be used for early detection.
authors.affiliation: Center for Health Disparities and Molecular Medicine, Department of Biochemistry and Microbiology, Loma Linda University, Loma Linda, California, United States of America.
authors.forename: Salma
authors.initials: S
authors.lastname: Khan
authors.forename: Jessica M S
authors.initials: JM
authors.lastname: Jutzy
authors.forename: Malyn May A
authors.initials: MM
authors.lastname: Valenzuela
authors.forename: David
authors.initials: D
authors.lastname: Turay
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Aspe
authors.forename: Arjun
authors.initials: A
authors.lastname: Ashok
authors.forename: Saied
authors.initials: S
authors.lastname: Mirshahidi
authors.forename: Dan
authors.initials: D
authors.lastname: Mercola
authors.forename: Michael B
authors.initials: MB
authors.lastname: Lilly
authors.forename: Nathan R
authors.initials: NR
authors.lastname: Wall
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D018450:Disease Progression; D055088:Early Detection of Cancer; D055354:Exosomes / Q000378:metabolism*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000097:blood*; D008297:Male; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000097:blood; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood; D011470:Prostatic Hyperplasia / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; D017430:Prostate-Specific Antigen