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miR-19, miR-345, miR-519c-5p serum levels predict adverse pathology in prostate cancer patients eligible for active surveillance.

Wang SY, Shiboski S, Belair CD, Cooperberg MR, Simko JP, Stoppler H, Cowan J, Carroll PR, Blelloch R - PLoS ONE (2014)

Bottom Line: Also, when combined with the CAPRA risk model the miRNA signature significantly enhanced prediction of patients with Gleason 7 disease.In-situ hybridizations of matching tumors showed miR-19 upregulation in transformed versus normal-appearing tumor epithelial, but independent of tumor grade suggesting an alternative source for the increase in serum miR-19a/b levels or the release of pre-existing intracellular miR-19a/b upon progression.It will be important to validate these findings in a larger multi-institutional study as well as with independent methodologies.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California, United States of America.

ABSTRACT
Serum microRNAs hold great promise as easily accessible and measurable biomarkers of disease. In prostate cancer, serum miRNA signatures have been associated with the presence of disease as well as correlated with previously validated risk models. However, it is unclear whether miRNAs can provide independent prognostic information beyond current risk models. Here, we focus on a group of low-risk prostate cancer patients who were eligible for active surveillance, but chose surgery. A major criteria for the low risk category is a Gleason score of 6 or lower based on pre-surgical biopsy. However, a third of these patients are upgraded to Gleason 7 on post surgical pathological analysis. Both in a discovery and a validation cohort, we find that pre-surgical serum levels of miR-19, miR-345 and miR-519c-5p can help identify these patients independent of their pre-surgical age, PSA, stage, and percent biopsy involvement. A combination of the three miRNAs increased the area under a receiver operator characteristics curve from 0.77 to 0.94 (p<0.01). Also, when combined with the CAPRA risk model the miRNA signature significantly enhanced prediction of patients with Gleason 7 disease. In-situ hybridizations of matching tumors showed miR-19 upregulation in transformed versus normal-appearing tumor epithelial, but independent of tumor grade suggesting an alternative source for the increase in serum miR-19a/b levels or the release of pre-existing intracellular miR-19a/b upon progression. Together, these data show that serum miRNAs can predict relatively small steps in tumor progression improving the capacity to predict disease risk and, therefore, potentially drive clinical decisions in prostate cancer patients. It will be important to validate these findings in a larger multi-institutional study as well as with independent methodologies.

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Schematic of the study design.
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pone-0098597-g001: Schematic of the study design.

Mentions: Patients included in the study were those opting for immediate radical prostatectomy who met the UCSF low-risk criteria for AS including biopsy Gleason 2–6 (no pattern 4 or 5), PSA less than 10 ng/ml, less than 34% of biopsy cores involved, less than 50% involvement in any single core, and clinical T1–T2 stage disease. A pathologic Gleason score of 7 of higher is associated with an increased risk of PCa mortality [20] and, therefore, was used to define adverse pathology. The discovery cohort consisted of 48 patients with a post-surgical pathologic Gleason score of 7 or higher (case group) and 48 patients with a pathologic Gleason score of 6 (control group). A validation cohort consisted of 25 cases and 35 controls. Patients were chosen from available samples maintained in a UCSF tissue bank. Patients fitting criteria above were selected from the available pool based on a random integer generator. A schematic of the study design is depicted in Figure 1.


miR-19, miR-345, miR-519c-5p serum levels predict adverse pathology in prostate cancer patients eligible for active surveillance.

Wang SY, Shiboski S, Belair CD, Cooperberg MR, Simko JP, Stoppler H, Cowan J, Carroll PR, Blelloch R - PLoS ONE (2014)

Schematic of the study design.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4043973&req=5

pone-0098597-g001: Schematic of the study design.
Mentions: Patients included in the study were those opting for immediate radical prostatectomy who met the UCSF low-risk criteria for AS including biopsy Gleason 2–6 (no pattern 4 or 5), PSA less than 10 ng/ml, less than 34% of biopsy cores involved, less than 50% involvement in any single core, and clinical T1–T2 stage disease. A pathologic Gleason score of 7 of higher is associated with an increased risk of PCa mortality [20] and, therefore, was used to define adverse pathology. The discovery cohort consisted of 48 patients with a post-surgical pathologic Gleason score of 7 or higher (case group) and 48 patients with a pathologic Gleason score of 6 (control group). A validation cohort consisted of 25 cases and 35 controls. Patients were chosen from available samples maintained in a UCSF tissue bank. Patients fitting criteria above were selected from the available pool based on a random integer generator. A schematic of the study design is depicted in Figure 1.

Bottom Line: Also, when combined with the CAPRA risk model the miRNA signature significantly enhanced prediction of patients with Gleason 7 disease.In-situ hybridizations of matching tumors showed miR-19 upregulation in transformed versus normal-appearing tumor epithelial, but independent of tumor grade suggesting an alternative source for the increase in serum miR-19a/b levels or the release of pre-existing intracellular miR-19a/b upon progression.It will be important to validate these findings in a larger multi-institutional study as well as with independent methodologies.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California, United States of America.

ABSTRACT
Serum microRNAs hold great promise as easily accessible and measurable biomarkers of disease. In prostate cancer, serum miRNA signatures have been associated with the presence of disease as well as correlated with previously validated risk models. However, it is unclear whether miRNAs can provide independent prognostic information beyond current risk models. Here, we focus on a group of low-risk prostate cancer patients who were eligible for active surveillance, but chose surgery. A major criteria for the low risk category is a Gleason score of 6 or lower based on pre-surgical biopsy. However, a third of these patients are upgraded to Gleason 7 on post surgical pathological analysis. Both in a discovery and a validation cohort, we find that pre-surgical serum levels of miR-19, miR-345 and miR-519c-5p can help identify these patients independent of their pre-surgical age, PSA, stage, and percent biopsy involvement. A combination of the three miRNAs increased the area under a receiver operator characteristics curve from 0.77 to 0.94 (p<0.01). Also, when combined with the CAPRA risk model the miRNA signature significantly enhanced prediction of patients with Gleason 7 disease. In-situ hybridizations of matching tumors showed miR-19 upregulation in transformed versus normal-appearing tumor epithelial, but independent of tumor grade suggesting an alternative source for the increase in serum miR-19a/b levels or the release of pre-existing intracellular miR-19a/b upon progression. Together, these data show that serum miRNAs can predict relatively small steps in tumor progression improving the capacity to predict disease risk and, therefore, potentially drive clinical decisions in prostate cancer patients. It will be important to validate these findings in a larger multi-institutional study as well as with independent methodologies.

Show MeSH
Related in: MedlinePlus