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.Prostate Cancer and Prostatic Disease advance online publication, 7 January 2014; doi:10.1038/pcan.2013.57.
Written by:
Peng Z1, Skoog L2, Hellborg H3, Jonstam G4, Wingmo IL5, Hjälm-Eriksson M6, Harmenberg U6, Cedermark GC6, Andersson K7, Ahrlund-Richter L8, Pramana S9, Pawitan Y9, Nistér M2, Nilsson S6, Li C6 Are you the author?
1Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden. 2(1) Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden (2) Department of Clinical Pathology/Cytology, Karolinska University Hospital, Stockholm, Sweden. 3Regional Oncologic Center, Karolinska University Hospital, Stockholm, Sweden. 4Department of Clinical Oncology, Karolinska University Hospital, Stockholm, Sweden. 5Department of Clinical Pathology/Cytology, Karolinska University Hospital, Stockholm, Sweden. 6(1) Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden (2) Department of Clinical Oncology, Karolinska University Hospital, Stockholm, Sweden. 7Department of Oncology, Radiology and Radiation Sciences, Uppsala University, Uppsala, Sweden. 8Department of Women and Children's Health, Karolinska Institutet, Stockholm, Sweden. 9Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Reference: Prostate Cancer Prostatic Dis. 2014 Jan 7. (Epub ahead of print)
doi: 10.1038/pcan.2013.57
PubMed Abstract
PMID: 24394557
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