title: Microseminoprotein-Beta Expression in Different Stages of Prostate Cancer.
abstract: Microseminoprotein-beta (MSMB, MSMB) is an abundant secretory protein contributed by the prostate, and is implicated as a prostate cancer (PC) biomarker based on observations of its lower expression in cancerous cells compared with benign prostate epithelium. However, as the current literature on MSMB is inconsistent, we assessed the expression of MSMB at the protein and mRNA levels in a comprehensive set of different clinical stages of PC. Immunohistochemistry using monoclonal and polyclonal antibodies against MSMB was used to study protein expression in tissue specimens representing prostatectomies (n = 261) and in diagnostic needle biopsies from patients treated with androgen deprivation therapy (ADT) (n = 100), and in locally recurrent castration-resistant PC (CRPC) (n = 105) and CRPC metastases (n = 113). The transcript levels of MSMB, nuclear receptor co-activator 4 (NCOA4) and MSMB-NCOA4 fusion were examined by qRT-PCR in prostatectomy samples and by RNA-sequencing in benign prostatic hyperplasia, PC, and CRPC samples. We also measured serum MSMB levels and genotyped the single nucleotide polymorphism rs10993994 using DNA from the blood of 369 PC patients and 903 controls. MSMB expression in PC (29% of prostatectomies and 21% of needle biopsies) was more frequent than in CRPC (9% of locally recurrent CRPCs and 9% of CRPC metastases) (p<0.0001). Detection of MSMB protein was inversely correlated with the Gleason score in prostatectomy specimens (p = 0.024). The read-through MSMB-NCOA4 transcript was detected at very low levels in PC. MSMB levels in serum were similar in cases of PC and controls but were significantly associated with PC risk when adjusted for age at diagnosis and levels of free or total PSA (p<0.001). Serum levels of MSMB in both PC patients and controls were significantly associated with the rs10993994 genotype (p<0.0001). In conclusion, decreased expression of MSMB parallels the clinical progression of PC and adjusted serum MSMB levels are associated with PC risk.
authors.affiliation: Prostate Cancer Research Center, Institute of Biosciences and Medical Technology (BioMediTech), University of Tampere, Tampere, Finland.|Fimlab Laboratories, Tampere University Hospital, Tampere, Finland.
authors.forename: Liisa
authors.initials: L
authors.lastname: Sjöblom
authors.affiliation: Prostate Cancer Research Center, Institute of Biosciences and Medical Technology (BioMediTech), University of Tampere, Tampere, Finland.|Fimlab Laboratories, Tampere University Hospital, Tampere, Finland.
authors.forename: Outi
authors.initials: O
authors.lastname: Saramäki
authors.affiliation: Prostate Cancer Research Center, Institute of Biosciences and Medical Technology (BioMediTech), University of Tampere, Tampere, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Annala
authors.affiliation: Prostate Cancer Research Center, Institute of Biosciences and Medical Technology (BioMediTech), University of Tampere, Tampere, Finland.|Fimlab Laboratories, Tampere University Hospital, Tampere, Finland.
authors.forename: Katri
authors.initials: K
authors.lastname: Leinonen
authors.affiliation: Prostate Cancer Research Center, Institute of Biosciences and Medical Technology (BioMediTech), University of Tampere, Tampere, Finland.
authors.forename: Janika
authors.initials: J
authors.lastname: Nättinen
authors.affiliation: Department of Pathology, Fimlab Laboratories, Tampere University Hospital, Tampere, Finland.
authors.forename: Teemu
authors.initials: T
authors.lastname: Tolonen
authors.affiliation: Prostate Cancer Research Center, Institute of Biosciences and Medical Technology (BioMediTech), University of Tampere, Tampere, Finland.
authors.forename: Tiina
authors.initials: T
authors.lastname: Wahlfors
authors.affiliation: Prostate Cancer Research Center, Institute of Biosciences and Medical Technology (BioMediTech), University of Tampere, Tampere, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Nykter
authors.affiliation: Prostate Cancer Research Center, Institute of Biosciences and Medical Technology (BioMediTech), University of Tampere, Tampere, Finland.
authors.forename: G Steven
authors.initials: GS
authors.lastname: Bova
authors.affiliation: Prostate Cancer Research Center, Institute of Biosciences and Medical Technology (BioMediTech), University of Tampere, Tampere, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Schleutker
authors.affiliation: Prostate Cancer Research Center, School of Medicine, University of Tampere, Tampere, Finland.|Department of Urology, Tampere University Hospital, Tampere, Finland.
authors.forename: Teuvo L J
authors.initials: TL
authors.lastname: Tammela
authors.affiliation: Prostate Cancer Research Center, Institute of Biosciences and Medical Technology (BioMediTech), University of Tampere, Tampere, Finland.|Departments of Laboratory Medicine, Surgery, and Medicine, Memorial Sloan Kettering Cancer Center, New York, United States of America.|Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom.|Department of Translational Medicine, Lund University, Malmö, Sweden.
authors.forename: Hans
authors.initials: H
authors.lastname: Lilja
authors.affiliation: Prostate Cancer Research Center, Institute of Biosciences and Medical Technology (BioMediTech), University of Tampere, Tampere, Finland.|Fimlab Laboratories, Tampere University Hospital, Tampere, Finland.
authors.forename: Tapio
authors.initials: T
authors.lastname: Visakorpi
mesh_terms: D000728:Androgens / Q000378:metabolism; D001707:Biopsy, Needle; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000097:blood / Q000378:metabolism; D009364:Neoplasm Recurrence, Local; D056918:Nuclear Receptor Coactivators / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011468:Prostatectomy; D011470:Prostatic Hyperplasia / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000097:blood* / Q000378:metabolism*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood* / Q000378:metabolism*; D029584:Prostatic Secretory Proteins / Q000097:blood* / Q000378:metabolism*; D017423:Sequence Analysis, RNA
chemical_list: D000728:Androgens; C111382:NCOA4 protein, human; D009363:Neoplasm Proteins; D056918:Nuclear Receptor Coactivators; D029584:Prostatic Secretory Proteins; C043076:beta-microseminoprotein