Validation of the four-miRNA biomarker panel MiCaP for prediction of long-term prostate cancer outcome
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
Validation of the four-miRNA biomarker panel MiCaP for prediction of long-term prostate cancer outcome. / Strand, Siri H; Schmidt, Linnéa; Weiss, Simone; Borre, Michael; Kristensen, Helle; Rasmussen, Anne Karin Ildor; Daugaard, Tina Fuglsang; Kristensen, Gitte; Stroomberg, Hein Vincent; Røder, Martin Andreas; Brasso, Klaus; Mouritzen, Peter; Sørensen, Karina Dalsgaard.
I: Scientific Reports, Bind 10, 10704, 2020.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Validation of the four-miRNA biomarker panel MiCaP for prediction of long-term prostate cancer outcome
AU - Strand, Siri H
AU - Schmidt, Linnéa
AU - Weiss, Simone
AU - Borre, Michael
AU - Kristensen, Helle
AU - Rasmussen, Anne Karin Ildor
AU - Daugaard, Tina Fuglsang
AU - Kristensen, Gitte
AU - Stroomberg, Hein Vincent
AU - Røder, Martin Andreas
AU - Brasso, Klaus
AU - Mouritzen, Peter
AU - Sørensen, Karina Dalsgaard
PY - 2020
Y1 - 2020
N2 - Improved prostate cancer prognostic biomarkers are urgently needed. We previously identified the four-miRNA prognostic biomarker panel MiCaP ((miR-23a-3p × miR-10b-5p)/(miR-133a-3p × miR-374b-5p)) for prediction of biochemical recurrence (BCR) after radical prostatectomy (RP). Here, we identified an optimal numerical cut-off for MiCaP dichotomisation using a training cohort of 475 RP patients and tested this in an independent cohort of 281 RP patients (PCA281). Kaplan-Meier, uni- and multivariate Cox regression analyses were conducted for multiple endpoints: BCR, metastatic-(mPC) and castration-resistant prostate cancer (CRPC), prostate cancer-specific (PCSS) and overall survival (OS). Functional effects of the four MiCaP miRNAs were assessed by overexpression and inhibition experiments in prostate cancer cell lines. We found the numerical value 5.709 optimal for MiCaP dichotomisation. This was independently validated in PCA281, where a high MiCaP score significantly [and independent of the Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) score] predicted BCR, progression to mPC and CRPC, and PCSS, but not OS. Harrell's C-index increased upon addition of MiCaP to CAPRA-S for all endpoints. Inhibition of miR-23a-3p and miR-10b-5p, and overexpression of miR-133a-3p and miR-374b-5p significantly reduced cell survival. Our results may promote future implementation of a MiCaP-based test for improved prostate cancer risk stratification.
AB - Improved prostate cancer prognostic biomarkers are urgently needed. We previously identified the four-miRNA prognostic biomarker panel MiCaP ((miR-23a-3p × miR-10b-5p)/(miR-133a-3p × miR-374b-5p)) for prediction of biochemical recurrence (BCR) after radical prostatectomy (RP). Here, we identified an optimal numerical cut-off for MiCaP dichotomisation using a training cohort of 475 RP patients and tested this in an independent cohort of 281 RP patients (PCA281). Kaplan-Meier, uni- and multivariate Cox regression analyses were conducted for multiple endpoints: BCR, metastatic-(mPC) and castration-resistant prostate cancer (CRPC), prostate cancer-specific (PCSS) and overall survival (OS). Functional effects of the four MiCaP miRNAs were assessed by overexpression and inhibition experiments in prostate cancer cell lines. We found the numerical value 5.709 optimal for MiCaP dichotomisation. This was independently validated in PCA281, where a high MiCaP score significantly [and independent of the Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) score] predicted BCR, progression to mPC and CRPC, and PCSS, but not OS. Harrell's C-index increased upon addition of MiCaP to CAPRA-S for all endpoints. Inhibition of miR-23a-3p and miR-10b-5p, and overexpression of miR-133a-3p and miR-374b-5p significantly reduced cell survival. Our results may promote future implementation of a MiCaP-based test for improved prostate cancer risk stratification.
KW - Biomarkers, Tumor/genetics
KW - Cell Line, Tumor
KW - Cell Survival/genetics
KW - Gene Expression Profiling
KW - Humans
KW - Male
KW - MicroRNAs/genetics
KW - Prognosis
KW - Prostate/pathology
KW - Prostatectomy
KW - Prostatic Neoplasms, Castration-Resistant/genetics
U2 - 10.1038/s41598-020-67320-y
DO - 10.1038/s41598-020-67320-y
M3 - Journal article
C2 - 32612164
VL - 10
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 10704
ER -
ID: 257037764