Profiling of Circulating microRNAs in Prostate Cancer Reveals Diagnostic Biomarker Potential

Jacob Fredsøe; Anne K. I. Rasmussen; Peter Mouritzen; Marianne T. Bjerre; Peter Østergren; Mikkel Fode; Michael Borre; Karina Dalsgaard Sørensen

doi:10.3390/diagnostics10040188

Profiling of Circulating microRNAs in Prostate Cancer Reveals Diagnostic Biomarker Potential

Jacob Fredsøe, Anne K. I. Rasmussen, Peter Mouritzen, Marianne T. Bjerre, Peter Østergren, Mikkel Fode, Michael Borre, Karina Dalsgaard Sørensen

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

21 Citationer (Scopus)

Abstract

Early detection of prostate cancer (PC) is paramount as localized disease is generally curable, while metastatic PC is generally incurable. There is a need for improved, minimally invasive biomarkers as current diagnostic tools are inaccurate, leading to extensive overtreatment while still missing some clinically significant cancers. Consequently, we profiled the expression levels of 92 selected microRNAs by RT-qPCR in plasma samples from 753 patients, representing multiple stages of PC and non-cancer controls. First, we compared plasma miRNA levels in patients with benign prostatic hyperplasia (BPH) or localized prostate cancer (LPC), versus advanced prostate cancer (APC). We identified several dysregulated microRNAs with a large overlap of 59 up/down-regulated microRNAs between BPH versus APC and LPC versus APC. Besides identifying several novel PC-associated dysregulated microRNAsin plasma, weconfirmed the previously reported upregulation of miR-375 and downregulation of miR-146a-5p. Next, by randomly splitting our dataset into a training and test set, we identified and successfully validated a novel four microRNA diagnostic ratio model, termed bCaP (miR-375∗miR-33a-5p/miR-16-5p∗miR-409-3p). Combined in a model with prostate specific antigen (PSA), digital rectal examination status, and age, bCaP predicted the outcomes of transrectal ultrasound (TRUS)-guided biopsies (negative vs. positive) with greater accuracy than PSA alone (Training: area under the curve (AUC), model = 0.84; AUC, PSA = 0.63. Test set: AUC, model = 0.67; AUC, PSA = 0.56). It may be possible in the future to use this simple and minimally invasive bCaP test in combination with existing clinical parameters for a more accurate selection of patients for prostate biopsy.

Originalsprog	Engelsk
Artikelnummer	188
Tidsskrift	Diagnostics
Vol/bind	10
Nummer	4
Antal sider	13
DOI	https://doi.org/10.3390/diagnostics10040188
Status	Udgivet - 2020

Adgang til dokumentet

10.3390/diagnostics10040188Licens: CC BY

Andre filer og links

http://www.scopus.com/inward/record.url?scp=85082748162&partnerID=8YFLogxK

Citationsformater

@article{e1460ff91d1d421abd35ce8c07843d7d,

title = "Profiling of Circulating microRNAs in Prostate Cancer Reveals Diagnostic Biomarker Potential",

abstract = "Early detection of prostate cancer (PC) is paramount as localized disease is generally curable, while metastatic PC is generally incurable. There is a need for improved, minimally invasive biomarkers as current diagnostic tools are inaccurate, leading to extensive overtreatment while still missing some clinically significant cancers. Consequently, we profiled the expression levels of 92 selected microRNAs by RT-qPCR in plasma samples from 753 patients, representing multiple stages of PC and non-cancer controls. First, we compared plasma miRNA levels in patients with benign prostatic hyperplasia (BPH) or localized prostate cancer (LPC), versus advanced prostate cancer (APC). We identified several dysregulated microRNAs with a large overlap of 59 up/down-regulated microRNAs between BPH versus APC and LPC versus APC. Besides identifying several novel PC-associated dysregulated microRNAsin plasma, weconfirmed the previously reported upregulation of miR-375 and downregulation of miR-146a-5p. Next, by randomly splitting our dataset into a training and test set, we identified and successfully validated a novel four microRNA diagnostic ratio model, termed bCaP (miR-375∗miR-33a-5p/miR-16-5p∗miR-409-3p). Combined in a model with prostate specific antigen (PSA), digital rectal examination status, and age, bCaP predicted the outcomes of transrectal ultrasound (TRUS)-guided biopsies (negative vs. positive) with greater accuracy than PSA alone (Training: area under the curve (AUC), model = 0.84; AUC, PSA = 0.63. Test set: AUC, model = 0.67; AUC, PSA = 0.56). It may be possible in the future to use this simple and minimally invasive bCaP test in combination with existing clinical parameters for a more accurate selection of patients for prostate biopsy.",

keywords = "BCaP, Biomarker, Diagnosis, MicroRNA, Plasma, Prostate cancer",

author = "Jacob Freds{\o}e and Rasmussen, {Anne K. I.} and Peter Mouritzen and Bjerre, {Marianne T.} and Peter {\O}stergren and Mikkel Fode and Michael Borre and S{\o}rensen, {Karina Dalsgaard}",

year = "2020",

doi = "10.3390/diagnostics10040188",

language = "English",

volume = "10",

journal = "Diagnostics",

publisher = "MDPI AG",

number = "4",

}

TY - JOUR

T1 - Profiling of Circulating microRNAs in Prostate Cancer Reveals Diagnostic Biomarker Potential

AU - Fredsøe, Jacob

AU - Rasmussen, Anne K. I.

AU - Mouritzen, Peter

AU - Bjerre, Marianne T.

AU - Østergren, Peter

AU - Fode, Mikkel

AU - Borre, Michael

AU - Sørensen, Karina Dalsgaard

PY - 2020

Y1 - 2020

N2 - Early detection of prostate cancer (PC) is paramount as localized disease is generally curable, while metastatic PC is generally incurable. There is a need for improved, minimally invasive biomarkers as current diagnostic tools are inaccurate, leading to extensive overtreatment while still missing some clinically significant cancers. Consequently, we profiled the expression levels of 92 selected microRNAs by RT-qPCR in plasma samples from 753 patients, representing multiple stages of PC and non-cancer controls. First, we compared plasma miRNA levels in patients with benign prostatic hyperplasia (BPH) or localized prostate cancer (LPC), versus advanced prostate cancer (APC). We identified several dysregulated microRNAs with a large overlap of 59 up/down-regulated microRNAs between BPH versus APC and LPC versus APC. Besides identifying several novel PC-associated dysregulated microRNAsin plasma, weconfirmed the previously reported upregulation of miR-375 and downregulation of miR-146a-5p. Next, by randomly splitting our dataset into a training and test set, we identified and successfully validated a novel four microRNA diagnostic ratio model, termed bCaP (miR-375∗miR-33a-5p/miR-16-5p∗miR-409-3p). Combined in a model with prostate specific antigen (PSA), digital rectal examination status, and age, bCaP predicted the outcomes of transrectal ultrasound (TRUS)-guided biopsies (negative vs. positive) with greater accuracy than PSA alone (Training: area under the curve (AUC), model = 0.84; AUC, PSA = 0.63. Test set: AUC, model = 0.67; AUC, PSA = 0.56). It may be possible in the future to use this simple and minimally invasive bCaP test in combination with existing clinical parameters for a more accurate selection of patients for prostate biopsy.

AB - Early detection of prostate cancer (PC) is paramount as localized disease is generally curable, while metastatic PC is generally incurable. There is a need for improved, minimally invasive biomarkers as current diagnostic tools are inaccurate, leading to extensive overtreatment while still missing some clinically significant cancers. Consequently, we profiled the expression levels of 92 selected microRNAs by RT-qPCR in plasma samples from 753 patients, representing multiple stages of PC and non-cancer controls. First, we compared plasma miRNA levels in patients with benign prostatic hyperplasia (BPH) or localized prostate cancer (LPC), versus advanced prostate cancer (APC). We identified several dysregulated microRNAs with a large overlap of 59 up/down-regulated microRNAs between BPH versus APC and LPC versus APC. Besides identifying several novel PC-associated dysregulated microRNAsin plasma, weconfirmed the previously reported upregulation of miR-375 and downregulation of miR-146a-5p. Next, by randomly splitting our dataset into a training and test set, we identified and successfully validated a novel four microRNA diagnostic ratio model, termed bCaP (miR-375∗miR-33a-5p/miR-16-5p∗miR-409-3p). Combined in a model with prostate specific antigen (PSA), digital rectal examination status, and age, bCaP predicted the outcomes of transrectal ultrasound (TRUS)-guided biopsies (negative vs. positive) with greater accuracy than PSA alone (Training: area under the curve (AUC), model = 0.84; AUC, PSA = 0.63. Test set: AUC, model = 0.67; AUC, PSA = 0.56). It may be possible in the future to use this simple and minimally invasive bCaP test in combination with existing clinical parameters for a more accurate selection of patients for prostate biopsy.

KW - BCaP

KW - Biomarker

KW - Diagnosis

KW - MicroRNA

KW - Plasma

KW - Prostate cancer

UR - http://www.scopus.com/inward/record.url?scp=85082748162&partnerID=8YFLogxK

U2 - 10.3390/diagnostics10040188

DO - 10.3390/diagnostics10040188

M3 - Journal article

C2 - 32231021

VL - 10

JO - Diagnostics

JF - Diagnostics

IS - 4

M1 - 188

ER -

Profiling of Circulating microRNAs in Prostate Cancer Reveals Diagnostic Biomarker Potential

Abstract

Adgang til dokumentet

Andre filer og links

Fingeraftryk

Citationsformater