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A novel miRNA-based predictive model for biochemical failure following post-prostatectomy salvage radiation therapy.

Bell EH, Kirste S, Fleming JL, Stegmaier P, Drendel V, Mo X, Ling S, Fabian D, Manring I, Jilg CA, Schultze-Seemann W, McNulty M, Zynger DL, Martin D, White J, Werner M, Grosu AL, Chakravarti A - PLoS ONE (2015)

Bottom Line: Univariate and multivariate Cox proportion hazards regression models as well as receiver operating characteristics were used to identify statistically significant miRNAs that were predictive of biochemical recurrence.Eighty eight miRNAs were identified to be significantly (p<0.05) associated with biochemical failure post-prostatectomy by multivariate analysis and clustered into two groups that correlated with early (≤ 36 months) versus late recurrence (>36 months).Both findings warrant further validation studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiation Oncology, Arthur G. James Hospital/ Ohio State Comprehensive Cancer Center, Columbus, Ohio, United States of America.

ABSTRACT

Purpose: To develop a microRNA (miRNA)-based predictive model for prostate cancer patients of 1) time to biochemical recurrence after radical prostatectomy and 2) biochemical recurrence after salvage radiation therapy following documented biochemical disease progression post-radical prostatectomy.

Methods: Forty three patients who had undergone salvage radiation therapy following biochemical failure after radical prostatectomy with greater than 4 years of follow-up data were identified. Formalin-fixed, paraffin-embedded tissue blocks were collected for all patients and total RNA was isolated from 1mm cores enriched for tumor (>70%). Eight hundred miRNAs were analyzed simultaneously using the nCounter human miRNA v2 assay (NanoString Technologies; Seattle, WA). Univariate and multivariate Cox proportion hazards regression models as well as receiver operating characteristics were used to identify statistically significant miRNAs that were predictive of biochemical recurrence.

Results: Eighty eight miRNAs were identified to be significantly (p<0.05) associated with biochemical failure post-prostatectomy by multivariate analysis and clustered into two groups that correlated with early (≤ 36 months) versus late recurrence (>36 months). Nine miRNAs were identified to be significantly (p<0.05) associated by multivariate analysis with biochemical failure after salvage radiation therapy. A new predictive model for biochemical recurrence after salvage radiation therapy was developed; this model consisted of miR-4516 and miR-601 together with, Gleason score, and lymph node status. The area under the ROC curve (AUC) was improved to 0.83 compared to that of 0.66 for Gleason score and lymph node status alone.

Conclusion: miRNA signatures can distinguish patients who fail soon after radical prostatectomy versus late failures, giving insight into which patients may need adjuvant therapy. Notably, two novel miRNAs (miR-4516 and miR-601) were identified that significantly improve prediction of biochemical failure post-salvage radiation therapy compared to clinico-histopathological factors, supporting the use of miRNAs within clinically used predictive models. Both findings warrant further validation studies.

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Related in: MedlinePlus

Study design.All patients underwent radical prostatectomy and salvage radiation therapy following biochemical recurrence. Tissue isolated at the time of radical prostatectomy (n = 43) was used for miRNA profiling.
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pone.0118745.g001: Study design.All patients underwent radical prostatectomy and salvage radiation therapy following biochemical recurrence. Tissue isolated at the time of radical prostatectomy (n = 43) was used for miRNA profiling.

Mentions: Univariate Analysis. A schematic of the study design is shown in Fig. 1. A clinical database was established for 43 PCa patients who underwent both RP and salvage RT (Table 1). Risk factors included 32.5% of patients who had a Gleason score of 8 or above, 25.6% of patients who had seminal vesicle invasion or extraprostatic extension, and 41.9% of patients who had positive margins. Salvage RT was started at a median PSA value of 0.39 ng/ml. Nineteen patients (44.2%) experienced BF after salvage RT at a median time of 27.1 months (range 0.0–64.1 months). The median follow-up times after RP and after salvage RT were 6.9 and 3.7 years, respectively.


A novel miRNA-based predictive model for biochemical failure following post-prostatectomy salvage radiation therapy.

Bell EH, Kirste S, Fleming JL, Stegmaier P, Drendel V, Mo X, Ling S, Fabian D, Manring I, Jilg CA, Schultze-Seemann W, McNulty M, Zynger DL, Martin D, White J, Werner M, Grosu AL, Chakravarti A - PLoS ONE (2015)

Study design.All patients underwent radical prostatectomy and salvage radiation therapy following biochemical recurrence. Tissue isolated at the time of radical prostatectomy (n = 43) was used for miRNA profiling.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4356539&req=5

pone.0118745.g001: Study design.All patients underwent radical prostatectomy and salvage radiation therapy following biochemical recurrence. Tissue isolated at the time of radical prostatectomy (n = 43) was used for miRNA profiling.
Mentions: Univariate Analysis. A schematic of the study design is shown in Fig. 1. A clinical database was established for 43 PCa patients who underwent both RP and salvage RT (Table 1). Risk factors included 32.5% of patients who had a Gleason score of 8 or above, 25.6% of patients who had seminal vesicle invasion or extraprostatic extension, and 41.9% of patients who had positive margins. Salvage RT was started at a median PSA value of 0.39 ng/ml. Nineteen patients (44.2%) experienced BF after salvage RT at a median time of 27.1 months (range 0.0–64.1 months). The median follow-up times after RP and after salvage RT were 6.9 and 3.7 years, respectively.

Bottom Line: Univariate and multivariate Cox proportion hazards regression models as well as receiver operating characteristics were used to identify statistically significant miRNAs that were predictive of biochemical recurrence.Eighty eight miRNAs were identified to be significantly (p<0.05) associated with biochemical failure post-prostatectomy by multivariate analysis and clustered into two groups that correlated with early (≤ 36 months) versus late recurrence (>36 months).Both findings warrant further validation studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiation Oncology, Arthur G. James Hospital/ Ohio State Comprehensive Cancer Center, Columbus, Ohio, United States of America.

ABSTRACT

Purpose: To develop a microRNA (miRNA)-based predictive model for prostate cancer patients of 1) time to biochemical recurrence after radical prostatectomy and 2) biochemical recurrence after salvage radiation therapy following documented biochemical disease progression post-radical prostatectomy.

Methods: Forty three patients who had undergone salvage radiation therapy following biochemical failure after radical prostatectomy with greater than 4 years of follow-up data were identified. Formalin-fixed, paraffin-embedded tissue blocks were collected for all patients and total RNA was isolated from 1mm cores enriched for tumor (>70%). Eight hundred miRNAs were analyzed simultaneously using the nCounter human miRNA v2 assay (NanoString Technologies; Seattle, WA). Univariate and multivariate Cox proportion hazards regression models as well as receiver operating characteristics were used to identify statistically significant miRNAs that were predictive of biochemical recurrence.

Results: Eighty eight miRNAs were identified to be significantly (p<0.05) associated with biochemical failure post-prostatectomy by multivariate analysis and clustered into two groups that correlated with early (≤ 36 months) versus late recurrence (>36 months). Nine miRNAs were identified to be significantly (p<0.05) associated by multivariate analysis with biochemical failure after salvage radiation therapy. A new predictive model for biochemical recurrence after salvage radiation therapy was developed; this model consisted of miR-4516 and miR-601 together with, Gleason score, and lymph node status. The area under the ROC curve (AUC) was improved to 0.83 compared to that of 0.66 for Gleason score and lymph node status alone.

Conclusion: miRNA signatures can distinguish patients who fail soon after radical prostatectomy versus late failures, giving insight into which patients may need adjuvant therapy. Notably, two novel miRNAs (miR-4516 and miR-601) were identified that significantly improve prediction of biochemical failure post-salvage radiation therapy compared to clinico-histopathological factors, supporting the use of miRNAs within clinically used predictive models. Both findings warrant further validation studies.

Show MeSH
Related in: MedlinePlus