title: HSD17B4 overexpression, an independent biomarker of poor patient outcome in prostate cancer.
abstract: Steroid hormones and their metabolising enzymes have been studied extensively for their potential role in prostate cancer, with more recent interest in the androgen/estrogen inactivating enzyme 17beta-hydroxysteroid dehydrogenase type 4 (HSD17B4). Gene expression profiling showed HSD17B4 to be significantly overexpressed in prostate cancer compared to matched-benign epithelium. We therefore hypothesized that altered HSD17B4 expression may contribute to prostate cancer progression via altered hormone balance. In this study, HSD17B4 mRNA and protein expression were assessed by in situ hybridisation (ISH) and immunohistochemistry (IHC), respectively, in tissue arrays of prostate tissue from 172 patients treated by radical prostatectomy. Overexpression of HSD17B4 mRNA and protein was associated with prostate cancer (P<0.0001) and multivariate Cox proportional hazards analysis, adjusted for known prognostic indicators, demonstrated HSD17B4 mRNA and high protein expression were significant independent predictors of poor patient outcome as measured by time until PSA relapse (mRNA: hazards ratio [HR]=1.90, 95% confidence interval [CI]=1.15-3.12; P<0.0001; and protein: HR=2.09, 95% CI=1.31-3.33; P=0.0026). Here we provide strong evidence that both mRNA and protein overexpression of HSD17B4 is not only associated with the presence of prostate cancer, but is also a significant independent predictor of poor patient outcome.
authors.affiliation: Cancer Research Program, Garvan Institute of Medical Research, St Vincent's Hospital, Darlinghurst, Sydney, NSW, Australia.
authors.forename: Krishan K
authors.initials: KK
authors.lastname: Rasiah
authors.forename: Margaret
authors.initials: M
authors.lastname: Gardiner-Garden
authors.forename: Emma J D
authors.initials: EJ
authors.lastname: Padilla
authors.forename: Gabriele
authors.initials: G
authors.lastname: Möller
authors.forename: James G
authors.initials: JG
authors.lastname: Kench
authors.forename: M Chehani
authors.initials: MC
authors.lastname: Alles
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Eggleton
authors.forename: Phillip D
authors.initials: PD
authors.lastname: Stricker
authors.forename: Jerzy
authors.initials: J
authors.lastname: Adamski
authors.forename: Robert L
authors.initials: RL
authors.lastname: Sutherland
authors.forename: Susan M
authors.initials: SM
authors.lastname: Henshall
authors.forename: Vanessa M
authors.initials: VM
authors.lastname: Hayes
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006836:Hydro-Lyases / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D064029:Peroxisomal Multifunctional Protein-2; D016016:Proportional Hazards Models; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013256:Steroids / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D013256:Steroids; D015067:17-Hydroxysteroid Dehydrogenases; D006836:Hydro-Lyases; D064029:Peroxisomal Multifunctional Protein-2; C104587:HSD17B4 protein, human