title: An expression signature at diagnosis to estimate prostate cancer patients' overall survival.
abstract: BACKGROUND
  This study aimed to identify biomarkers for estimating the overall and prostate cancer (PCa)-specific survival in PCa patients at diagnosis.
  
  
  METHODS
  To explore the importance of embryonic stem cell (ESC) gene signatures, we identified 641 ESC gene predictors (ESCGPs) using published microarray data sets. ESCGPs were selected in a stepwise manner, and were combined with reported genes. Selected genes were analyzed by multiplex quantitative polymerase chain reaction using prostate fine-needle aspiration samples taken at diagnosis from a Swedish cohort of 189 PCa patients diagnosed between 1986 and 2001. Of these patients, there was overall and PCa-specific survival data available for 97.9%, and 77.9% were primarily treated by hormone therapy only. Univariate and multivariate Cox proportional hazard ratios and Kaplan-Meier plots were used for the survival analysis, and a k-nearest neighbor (kNN) algorithm for estimating overall survival.
  
  
  RESULTS
  An expression signature of VGLL3, IGFBP3 and F3 was shown sufficient to categorize the patients into high-, intermediate- and low-risk subtypes. The median overall survival times of the subtypes were 3.23, 4.00 and 9.85 years, respectively. The difference corresponded to hazard ratios of 5.86 (95% confidence interval (CI): 2.91-11.78, P<0.001) for the high-risk subtype and 3.45 (95% CI: 1.79-6.66, P<0.001) for the intermediate-risk compared with the low-risk subtype. The kNN models that included the gene expression signature outperformed the one designed on clinical parameters alone.
  
  
  CONCLUSIONS
  The expression signature can potentially be used to estimate overall survival time. When validated in future studies, it could be integrated in the routine clinical diagnostic and prognostic procedure of PCa for an optimal treatment decision based on the estimated survival benefit.
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Z
authors.initials: Z
authors.lastname: Peng
authors.affiliation: 1] Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden [2] Department of Clinical Pathology/Cytology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Skoog
authors.affiliation: Regional Oncologic Center, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Hellborg
authors.affiliation: Department of Clinical Oncology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Jonstam
authors.affiliation: Department of Clinical Pathology/Cytology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: I-L
authors.initials: IL
authors.lastname: Wingmo
authors.affiliation: 1] Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden [2] Department of Clinical Oncology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Hjälm-Eriksson
authors.affiliation: 1] Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden [2] Department of Clinical Oncology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: U
authors.initials: U
authors.lastname: Harmenberg
authors.affiliation: 1] Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden [2] Department of Clinical Oncology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: G C
authors.initials: GC
authors.lastname: Cedermark
authors.affiliation: Department of Oncology, Radiology and Radiation Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Andersson
authors.affiliation: Department of Women and Children's Health, Karolinska Institutet, Stockholm, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Ahrlund-Richter
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Pramana
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Y
authors.initials: Y
authors.lastname: Pawitan
authors.affiliation: 1] Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden [2] Department of Clinical Pathology/Cytology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Nistér
authors.affiliation: 1] Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden [2] Department of Clinical Oncology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Nilsson
authors.affiliation: 1] Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden [2] Department of Clinical Oncology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: C
authors.identifier: 000000034331079X
authors.initials: C
authors.lastname: Li
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality* / Q000628:therapy; D012372:ROC Curve; D015203:Reproducibility of Results; D059467:Transcriptome