title: Increased expression of fibroblast growth factor 13 in prostate cancer is associated with shortened time to biochemical recurrence after radical prostatectomy.
abstract: Fibroblast growth factor homologous factors (FHFs) belong to the fibroblast growth factor (FGF) superfamily, which plays an important role in prostate cancer (PCa). Mining of public database suggests that FGF13 (FHF2) mRNA expression is altered in over 30% of PCa cases. This study examined the FGF13 expression pattern in human PCa specimens and evaluated its potential as a biomarker for patient outcome after radical prostatectomy (RP). Immunohistochemistry (IHC) showed that FGF13 was detectable in the majority of human PCa samples, and FGF13 IHC scores were higher in high-grade prostatic intraepithelial neoplasia, in primary PCa and in metastatic PCa than in benign prostatic tissue. There was a significant association between high cytoplasmic FGF13 staining and a risk of biochemical recurrence (BCR) after RP. This was also evident in the intermediate to high-risk patient groups. In contrast, positive nuclear FGF13 staining along with low cytoplasmic FGF13 group showed a decreased BCR risk. Multivariate regression analysis indicated that high cytoplasmic FGF13 staining was associated with BCR and that this could serve as an independent prognostic marker in PCa. Several PCa cell lines showed increased FGF13 expression at the mRNA and protein levels compared to the immortalized prostate epithelial cell line PNT1a. Analysis of co-labeled cells suggested a possible interaction of FGF13 with α-tubulin and the voltage-gated sodium channel proteins (Na(V)s/VGSCs). Our data indicate that, for PCa patients after RP, FGF13 serves as a potential novel prognostic marker that improves prediction of BCR-free survival, in particular if combined with other clinical parameters.
authors.affiliation: Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku, Turku, Finland.
authors.forename: Lan
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku, Turku, Finland.
authors.forename: Mervi
authors.initials: M
authors.lastname: Toriseva
authors.affiliation: Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku, Turku, Finland.
authors.forename: Miikka
authors.initials: M
authors.lastname: Tuomala
authors.affiliation: Department of Urology, Turku University Hospital, Turku, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Seikkula
authors.affiliation: Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
authors.forename: Teresa
authors.initials: T
authors.lastname: Elo
authors.affiliation: Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku, Turku, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Tuomela
authors.affiliation: Department of Pathology, University of Turku, Turku, Finland.
authors.forename: Markku
authors.initials: M
authors.lastname: Kallajoki
authors.affiliation: Department of Pathology, Helsinki University Hospital (HUSLAB) and Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
authors.forename: Tuomas
authors.initials: T
authors.lastname: Mirtti
authors.affiliation: Department of Pathology, University of Turku, Turku, Finland.
authors.forename: Pekka
authors.initials: P
authors.lastname: Taimen
authors.affiliation: Department of Urology, Turku University Hospital, Turku, Finland.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Boström
authors.affiliation: Department of Pathology, University of Turku, Turku, Finland.
authors.forename: Kalle
authors.initials: K
authors.lastname: Alanen
authors.affiliation: Department of Pathology, University of Turku, Turku, Finland.
authors.forename: Martti
authors.initials: M
authors.lastname: Nurmi
authors.affiliation: Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku, Turku, Finland.|Turku Centre for Biotechnology, University of Turku, Turku, Finland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Nees
authors.affiliation: Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku, Turku, Finland.
authors.forename: Pirkko
authors.initials: P
authors.lastname: Härkönen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D018572:Disease-Free Survival; D005346:Fibroblast Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D011468:Prostatectomy / Q000009:adverse effects; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D012333:RNA, Messenger / Q000096:biosynthesis; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C108111:fibroblast growth factor 13; D005346:Fibroblast Growth Factors
keywords: FGF13; prognostic marker; prostate cancer