title: Molecular characterization of clear cell renal cell carcinoma identifies CSNK2A1, SPP1 and DEFB1 as promising novel prognostic markers.
abstract: The prognosis associated with clear cell renal carcinoma (ccRCC) can vary widely and novel molecular prognostic markers are needed to assess prognosis at an earlier stage. Several gene products have been investigated for this purpose, but none of them have been implemented in clinical practice. Here we hypothesized that we, using TaqMan® Array, could identify superior prognostic messenger RNA (mRNA)s in long-term follow-up. Messenger RNA level of 19 candidate genes was investigated in 97 patients with ccRCC. Three genes impacted significantly on prognosis in both univariate and multivariate analysis. In univariate analysis, CSNK2A1 was a strong indicator of a poor overall survival (OS) (HR = 5.01, p < 0.001), disease specific survival (DSS) (HR = 6.21, p = 0.007) and progression free survival (PFS) (HR = 5.93, p = 0.005). High expression of SPP1 was associated to poor PFS (HR = 4.41, p = 0.04). DEFB1 was associated with a better PFS (HR = 0.24, p = 0.006). In multivariate analysis, CSNK2A1 was associated to a worse OS (HR = 3.56, p = 0.008) and PFS (HR = 3.84, p = 0.005), whereas SPP1 was an independent predictor of a worse PFS (HR = 3.46, p = 0.007) and DEFB1 of a better PFS (HR = 0.37, p = 0.027). These results show that with TaqMan®) Array we could identify three superior gene products related to prognosis. Further studies are needed to elucidate the pathways and roles of these genes in renal cacer development.
authors.affiliation: Department of Clinical Pathology, Odense University Hospital, Odense, Denmark.|Department of Urology, Odense University Hospital, Odense, Denmark.
authors.forename: Maj
authors.initials: M
authors.lastname: Rabjerg
authors.affiliation: Novo Nordisk A/S, Hjørring, Denmark.
authors.forename: Henriette
authors.initials: H
authors.lastname: Bjerregaard
authors.affiliation: Department of Epidemiology, Biostatistics and Biodemography, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Halekoh
authors.affiliation: Institute of Molecular Medicine, Cardiovascular and Renal Research, University of Southern Denmark, Odense, Denmark.
authors.forename: Boye L
authors.initials: BL
authors.lastname: Jensen
authors.affiliation: Department of Urology, Odense University Hospital, Odense, Denmark.
authors.forename: Steen
authors.initials: S
authors.lastname: Walter
authors.affiliation: Department of Clinical Pathology, Odense University Hospital, Odense, Denmark.|Department of Urology, Odense University Hospital, Odense, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Marcussen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002292:Carcinoma, Renal Cell / Q000175:diagnosis* / Q000473:pathology; D047390:Casein Kinase II / Q000096:biosynthesis / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D053495:Osteopontin / Q000096:biosynthesis* / Q000235:genetics; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics; D017422:Sequence Analysis, DNA; D016019:Survival Analysis; D023083:beta-Defensins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C406407:DEFB1 protein, human; D012333:RNA, Messenger; C506895:SPP1 protein, human; D023083:beta-Defensins; D053495:Osteopontin; C570325:CSNK2A1 protein, human; D047390:Casein Kinase II
keywords: CSNK2A1; DEFB1; SPP1; Taqman Array; ccRCC; prognosis