Limits...
An expression signature at diagnosis to estimate prostate cancer patients' overall survival.

Peng Z, Skoog L, Hellborg H, Jonstam G, Wingmo IL, Hjälm-Eriksson M, Harmenberg U, Cedermark GC, Andersson K, Ahrlund-Richter L, Pramana S, Pawitan Y, Nistér M, Nilsson S, Li C - Prostate Cancer Prostatic Dis. (2014)

Bottom Line: 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 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.

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.

Show MeSH

Related in: MedlinePlus

Survival difference between the three tumor subtypes classified according to the embryonic stem cell gene predictor (ESCGP) signature in patients primarily treated with castration therapy. Of the 95 patients shown in Figure 2, 65 received castration therapy as their primary treatment. Within this group, clear survival differences could still be observed according to the three tumor subtypes classified based on the ESCGP signature. The overall (upper panel), PCa-specific (middle panel) and non-PCa-specific (lower panel) survival analyses of the three subtypes are shown by the Kaplan–Meier curves. The P-values for differences between each of the three tumor subtypes were calculated using a log-rank test. Besides the most significant difference between subtypes 1 and 3 shown in the figure, the other P-values between each two subtypes were P1–2=0.037*, P2–3=0.001* (a); P1–2=0.009*, P2–3=0.006* (b); P1–2=0.955, P2–3=0.076 (c). The overall survival rates at 5 years of follow-up were 13.6%, 36.0% and 77.8% for groups 1, 2 and 3, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3921673&req=5

fig3: Survival difference between the three tumor subtypes classified according to the embryonic stem cell gene predictor (ESCGP) signature in patients primarily treated with castration therapy. Of the 95 patients shown in Figure 2, 65 received castration therapy as their primary treatment. Within this group, clear survival differences could still be observed according to the three tumor subtypes classified based on the ESCGP signature. The overall (upper panel), PCa-specific (middle panel) and non-PCa-specific (lower panel) survival analyses of the three subtypes are shown by the Kaplan–Meier curves. The P-values for differences between each of the three tumor subtypes were calculated using a log-rank test. Besides the most significant difference between subtypes 1 and 3 shown in the figure, the other P-values between each two subtypes were P1–2=0.037*, P2–3=0.001* (a); P1–2=0.009*, P2–3=0.006* (b); P1–2=0.955, P2–3=0.076 (c). The overall survival rates at 5 years of follow-up were 13.6%, 36.0% and 77.8% for groups 1, 2 and 3, respectively.

Mentions: Of the 189 patients evaluated, 87 had data available for all clinical parameters (mainly patients in Subsets 1 and 3) and could be classified into subtypes according to the expression signatures of VGLL3, IGFBP3 and F3. The multivariate analysis for overall and PCa-specific survival revealed that the tumor subtype classification defined by the ESCGP signature was the most powerful survival indicator and further independent of age, PSA level, tumor grade and clinical stage (Table 4). The median overall survival time was 3.23 years for patients with the high-risk subtype, 4.00 years for the intermediate-risk subtype and 9.85 years for the low-risk subtype (Figure 2), and these values 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 subtype compared with the low-risk subtype (Table 4 and Figure 2). Kaplan–Meier plots further indicated a clear survival difference between the three subtypes classified using the ESCGP signature (Figure 2 and Supplementary Figures S4 and S5). The difference in overall survival was attributed to both PCa-specific and non-PCa-specific survival (Figure 2). Interestingly, the survival difference between the three tumor subtypes was maintained when only patients treated with hormone therapy were analyzed, and these differences were independent of all other clinical parameters (Figure 3 and Supplementary Figure S5). Results from separate analysis of the subgroup of patients with cardiovascular disease were in agreement with the results from the complete cohort.


An expression signature at diagnosis to estimate prostate cancer patients' overall survival.

Peng Z, Skoog L, Hellborg H, Jonstam G, Wingmo IL, Hjälm-Eriksson M, Harmenberg U, Cedermark GC, Andersson K, Ahrlund-Richter L, Pramana S, Pawitan Y, Nistér M, Nilsson S, Li C - Prostate Cancer Prostatic Dis. (2014)

Survival difference between the three tumor subtypes classified according to the embryonic stem cell gene predictor (ESCGP) signature in patients primarily treated with castration therapy. Of the 95 patients shown in Figure 2, 65 received castration therapy as their primary treatment. Within this group, clear survival differences could still be observed according to the three tumor subtypes classified based on the ESCGP signature. The overall (upper panel), PCa-specific (middle panel) and non-PCa-specific (lower panel) survival analyses of the three subtypes are shown by the Kaplan–Meier curves. The P-values for differences between each of the three tumor subtypes were calculated using a log-rank test. Besides the most significant difference between subtypes 1 and 3 shown in the figure, the other P-values between each two subtypes were P1–2=0.037*, P2–3=0.001* (a); P1–2=0.009*, P2–3=0.006* (b); P1–2=0.955, P2–3=0.076 (c). The overall survival rates at 5 years of follow-up were 13.6%, 36.0% and 77.8% for groups 1, 2 and 3, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3921673&req=5

fig3: Survival difference between the three tumor subtypes classified according to the embryonic stem cell gene predictor (ESCGP) signature in patients primarily treated with castration therapy. Of the 95 patients shown in Figure 2, 65 received castration therapy as their primary treatment. Within this group, clear survival differences could still be observed according to the three tumor subtypes classified based on the ESCGP signature. The overall (upper panel), PCa-specific (middle panel) and non-PCa-specific (lower panel) survival analyses of the three subtypes are shown by the Kaplan–Meier curves. The P-values for differences between each of the three tumor subtypes were calculated using a log-rank test. Besides the most significant difference between subtypes 1 and 3 shown in the figure, the other P-values between each two subtypes were P1–2=0.037*, P2–3=0.001* (a); P1–2=0.009*, P2–3=0.006* (b); P1–2=0.955, P2–3=0.076 (c). The overall survival rates at 5 years of follow-up were 13.6%, 36.0% and 77.8% for groups 1, 2 and 3, respectively.
Mentions: Of the 189 patients evaluated, 87 had data available for all clinical parameters (mainly patients in Subsets 1 and 3) and could be classified into subtypes according to the expression signatures of VGLL3, IGFBP3 and F3. The multivariate analysis for overall and PCa-specific survival revealed that the tumor subtype classification defined by the ESCGP signature was the most powerful survival indicator and further independent of age, PSA level, tumor grade and clinical stage (Table 4). The median overall survival time was 3.23 years for patients with the high-risk subtype, 4.00 years for the intermediate-risk subtype and 9.85 years for the low-risk subtype (Figure 2), and these values 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 subtype compared with the low-risk subtype (Table 4 and Figure 2). Kaplan–Meier plots further indicated a clear survival difference between the three subtypes classified using the ESCGP signature (Figure 2 and Supplementary Figures S4 and S5). The difference in overall survival was attributed to both PCa-specific and non-PCa-specific survival (Figure 2). Interestingly, the survival difference between the three tumor subtypes was maintained when only patients treated with hormone therapy were analyzed, and these differences were independent of all other clinical parameters (Figure 3 and Supplementary Figure S5). Results from separate analysis of the subgroup of patients with cardiovascular disease were in agreement with the results from the complete cohort.

Bottom Line: 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 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.

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.

Show MeSH
Related in: MedlinePlus