title: Multiple recognition assay reveals prostasomes as promising plasma biomarkers for prostate cancer.
abstract: Prostasomes are microvesicles (mean diameter, 150 nm) that are produced and secreted by normal and malignant prostate acinar cells. It has been hypothesized that invasive growth of malignant prostate cells may cause these microvesicles, normally released into seminal fluid, to appear in interstitial space and therewith into peripheral circulation. The suitability of prostasomes as blood biomarkers in patients with prostate cancer was tested by using an expanded variant of the proximity ligation assay (PLA). We developed an extremely sensitive and specific assay (4PLA) for detection of complex target structures such as microvesicles in which the target is first captured via an immobilized antibody and subsequently detected by using four other antibodies with attached DNA strands. The requirement for coincident binding by five antibodies to generate an amplifiable reporter results in both increased specificity and sensitivity. The assay successfully detected significantly elevated levels of prostasomes in blood samples from patients with prostate cancer before radical prostatectomy, compared with controls and men with benign biopsy results. The medians for prostasome levels in blood plasma of patients with prostate cancer were 2.5 to sevenfold higher compared with control samples in two independent studies, and the assay also distinguished patients with high and medium prostatectomy Gleason scores (8/9 and 7, respectively) from those with low score (≤ 6), thus reflecting disease aggressiveness. This approach that enables detection of prostasomes in peripheral blood may be useful for early diagnosis and assessment of prognosis in organ-confined prostate cancer.
authors.affiliation: Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, SE-751 24 Uppsala, Sweden.
authors.forename: Gholamreza
authors.initials: G
authors.lastname: Tavoosidana
authors.forename: Gunnar
authors.initials: G
authors.lastname: Ronquist
authors.forename: Spyros
authors.initials: S
authors.lastname: Darmanis
authors.forename: Junhong
authors.initials: J
authors.lastname: Yan
authors.forename: Lena
authors.initials: L
authors.lastname: Carlsson
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.forename: Tim
authors.initials: T
authors.lastname: Conze
authors.forename: Pia
authors.initials: P
authors.lastname: Ek
authors.forename: Axel
authors.initials: A
authors.lastname: Semjonow
authors.forename: Elke
authors.initials: E
authors.lastname: Eltze
authors.forename: Anders
authors.initials: A
authors.lastname: Larsson
authors.forename: Ulf D
authors.initials: UD
authors.lastname: Landegren
authors.forename: Masood
authors.initials: M
authors.lastname: Kamali-Moghaddam
mesh_terms: D000368:Aged; D000906:Antibodies; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D016022:Case-Control Studies; D055088:Early Detection of Cancer / Q000379:methods*; D006801:Humans; D007118:Immunoassay / Q000379:methods* / Q000592:standards; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000175:diagnosis*; D012661:Semen / Q000737:chemistry*; D012680:Sensitivity and Specificity; D022161:Transport Vesicles / Q000737:chemistry*
chemical_list: D000906:Antibodies; D015415:Biomarkers