Blood-Based Biomarkers of Aggressive Prostate Cancer

Men Long Liong, Chun Ren Lim, Hengxuan Yang, Samuel Chao, Chin Wei Bong, Wing Seng Leong, Prashanta Kumar Das, Chit Sin Loh, Ban Eng Lau, Choon Geok Yu, Edie Jian Jiek Ooi, Robert K. Nam, Paul D. Allen, Graeme S. Steele, Karl Wassmann, Jerome P. Richie, Choong Chin Liew

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Purpose: Prostate cancer is a bimodal disease with aggressive and indolent forms. Current prostate-specific-antigen testing and digital rectal examination screening provide ambiguous results leading to both under-and over-treatment. Accurate, consistent diagnosis is crucial to risk-stratify patients and facilitate clinical decision making as to treatment versus active surveillance. Diagnosis is currently achieved by needle biopsy, a painful procedure. Thus, there is a clinical need for a minimally-invasive test to determine prostate cancer aggressiveness. A blood sample to predict Gleason score, which is known to reflect aggressiveness of the cancer, could serve as such a test. Materials and Methods: Blood mRNA was isolated from North American and Malaysian prostate cancer patients/controls. Microarray analysis was conducted utilizing the Affymetrix U133 plus 2·0 platform. Expression profiles from 255 patients/controls generated 85 candidate biomarkers. Following quantitative real-time PCR (qRT-PCR) analysis, ten disease-associated biomarkers remained for paired statistical analysis and normalization. Results: Microarray analysis was conducted to identify 85 genes differentially expressed between aggressive prostate cancer (Gleason score ≥8) and controls. Expression of these genes was qRT-PCR verified. Statistical analysis yielded a final seven-gene panel evaluated as six gene-ratio duplexes. This molecular signature predicted as aggressive (ie, Gleason score ≥8) 55% of G6 samples, 49% of G7(3+4), 79% of G7(4+3) and 83% of G8-10, while rejecting 98% of controls. Conclusion: In this study, we have developed a novel, blood-based biomarker panel which can be used as the basis of a simple blood test to identify men with aggressive prostate cancer and thereby reduce the overdiagnosis and overtreatment that currently results from diagnosis using PSA alone. We discuss possible clinical uses of the panel to identify men more likely to benefit from biopsy and immediate therapy versus those more suited to an "active surveillance" strategy.

Original languageEnglish (US)
Article numbere45802
JournalPLoS One
Volume7
Issue number9
DOIs
StatePublished - Sep 28 2012
Externally publishedYes

Fingerprint

prostatic neoplasms
Biomarkers
Neoplasm Grading
biomarkers
Prostatic Neoplasms
Blood
Genes
Biopsy
blood
Microarray Analysis
Microarrays
Real-Time Polymerase Chain Reaction
Statistical methods
aggression
biopsy
quantitative polymerase chain reaction
Digital Rectal Examination
statistical analysis
prostate-specific antigen
Hematologic Tests

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Liong, M. L., Lim, C. R., Yang, H., Chao, S., Bong, C. W., Leong, W. S., ... Liew, C. C. (2012). Blood-Based Biomarkers of Aggressive Prostate Cancer. PLoS One, 7(9), [e45802]. https://doi.org/10.1371/journal.pone.0045802

Blood-Based Biomarkers of Aggressive Prostate Cancer. / Liong, Men Long; Lim, Chun Ren; Yang, Hengxuan; Chao, Samuel; Bong, Chin Wei; Leong, Wing Seng; Das, Prashanta Kumar; Loh, Chit Sin; Lau, Ban Eng; Yu, Choon Geok; Ooi, Edie Jian Jiek; Nam, Robert K.; Allen, Paul D.; Steele, Graeme S.; Wassmann, Karl; Richie, Jerome P.; Liew, Choong Chin.

In: PLoS One, Vol. 7, No. 9, e45802, 28.09.2012.

Research output: Contribution to journalArticle

Liong, ML, Lim, CR, Yang, H, Chao, S, Bong, CW, Leong, WS, Das, PK, Loh, CS, Lau, BE, Yu, CG, Ooi, EJJ, Nam, RK, Allen, PD, Steele, GS, Wassmann, K, Richie, JP & Liew, CC 2012, 'Blood-Based Biomarkers of Aggressive Prostate Cancer', PLoS One, vol. 7, no. 9, e45802. https://doi.org/10.1371/journal.pone.0045802
Liong ML, Lim CR, Yang H, Chao S, Bong CW, Leong WS et al. Blood-Based Biomarkers of Aggressive Prostate Cancer. PLoS One. 2012 Sep 28;7(9). e45802. https://doi.org/10.1371/journal.pone.0045802
Liong, Men Long ; Lim, Chun Ren ; Yang, Hengxuan ; Chao, Samuel ; Bong, Chin Wei ; Leong, Wing Seng ; Das, Prashanta Kumar ; Loh, Chit Sin ; Lau, Ban Eng ; Yu, Choon Geok ; Ooi, Edie Jian Jiek ; Nam, Robert K. ; Allen, Paul D. ; Steele, Graeme S. ; Wassmann, Karl ; Richie, Jerome P. ; Liew, Choong Chin. / Blood-Based Biomarkers of Aggressive Prostate Cancer. In: PLoS One. 2012 ; Vol. 7, No. 9.
@article{30413c8e41e541e28472926c1d8ffc58,
title = "Blood-Based Biomarkers of Aggressive Prostate Cancer",
abstract = "Purpose: Prostate cancer is a bimodal disease with aggressive and indolent forms. Current prostate-specific-antigen testing and digital rectal examination screening provide ambiguous results leading to both under-and over-treatment. Accurate, consistent diagnosis is crucial to risk-stratify patients and facilitate clinical decision making as to treatment versus active surveillance. Diagnosis is currently achieved by needle biopsy, a painful procedure. Thus, there is a clinical need for a minimally-invasive test to determine prostate cancer aggressiveness. A blood sample to predict Gleason score, which is known to reflect aggressiveness of the cancer, could serve as such a test. Materials and Methods: Blood mRNA was isolated from North American and Malaysian prostate cancer patients/controls. Microarray analysis was conducted utilizing the Affymetrix U133 plus 2·0 platform. Expression profiles from 255 patients/controls generated 85 candidate biomarkers. Following quantitative real-time PCR (qRT-PCR) analysis, ten disease-associated biomarkers remained for paired statistical analysis and normalization. Results: Microarray analysis was conducted to identify 85 genes differentially expressed between aggressive prostate cancer (Gleason score ≥8) and controls. Expression of these genes was qRT-PCR verified. Statistical analysis yielded a final seven-gene panel evaluated as six gene-ratio duplexes. This molecular signature predicted as aggressive (ie, Gleason score ≥8) 55{\%} of G6 samples, 49{\%} of G7(3+4), 79{\%} of G7(4+3) and 83{\%} of G8-10, while rejecting 98{\%} of controls. Conclusion: In this study, we have developed a novel, blood-based biomarker panel which can be used as the basis of a simple blood test to identify men with aggressive prostate cancer and thereby reduce the overdiagnosis and overtreatment that currently results from diagnosis using PSA alone. We discuss possible clinical uses of the panel to identify men more likely to benefit from biopsy and immediate therapy versus those more suited to an {"}active surveillance{"} strategy.",
author = "Liong, {Men Long} and Lim, {Chun Ren} and Hengxuan Yang and Samuel Chao and Bong, {Chin Wei} and Leong, {Wing Seng} and Das, {Prashanta Kumar} and Loh, {Chit Sin} and Lau, {Ban Eng} and Yu, {Choon Geok} and Ooi, {Edie Jian Jiek} and Nam, {Robert K.} and Allen, {Paul D.} and Steele, {Graeme S.} and Karl Wassmann and Richie, {Jerome P.} and Liew, {Choong Chin}",
year = "2012",
month = "9",
day = "28",
doi = "10.1371/journal.pone.0045802",
language = "English (US)",
volume = "7",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "9",

}

TY - JOUR

T1 - Blood-Based Biomarkers of Aggressive Prostate Cancer

AU - Liong, Men Long

AU - Lim, Chun Ren

AU - Yang, Hengxuan

AU - Chao, Samuel

AU - Bong, Chin Wei

AU - Leong, Wing Seng

AU - Das, Prashanta Kumar

AU - Loh, Chit Sin

AU - Lau, Ban Eng

AU - Yu, Choon Geok

AU - Ooi, Edie Jian Jiek

AU - Nam, Robert K.

AU - Allen, Paul D.

AU - Steele, Graeme S.

AU - Wassmann, Karl

AU - Richie, Jerome P.

AU - Liew, Choong Chin

PY - 2012/9/28

Y1 - 2012/9/28

N2 - Purpose: Prostate cancer is a bimodal disease with aggressive and indolent forms. Current prostate-specific-antigen testing and digital rectal examination screening provide ambiguous results leading to both under-and over-treatment. Accurate, consistent diagnosis is crucial to risk-stratify patients and facilitate clinical decision making as to treatment versus active surveillance. Diagnosis is currently achieved by needle biopsy, a painful procedure. Thus, there is a clinical need for a minimally-invasive test to determine prostate cancer aggressiveness. A blood sample to predict Gleason score, which is known to reflect aggressiveness of the cancer, could serve as such a test. Materials and Methods: Blood mRNA was isolated from North American and Malaysian prostate cancer patients/controls. Microarray analysis was conducted utilizing the Affymetrix U133 plus 2·0 platform. Expression profiles from 255 patients/controls generated 85 candidate biomarkers. Following quantitative real-time PCR (qRT-PCR) analysis, ten disease-associated biomarkers remained for paired statistical analysis and normalization. Results: Microarray analysis was conducted to identify 85 genes differentially expressed between aggressive prostate cancer (Gleason score ≥8) and controls. Expression of these genes was qRT-PCR verified. Statistical analysis yielded a final seven-gene panel evaluated as six gene-ratio duplexes. This molecular signature predicted as aggressive (ie, Gleason score ≥8) 55% of G6 samples, 49% of G7(3+4), 79% of G7(4+3) and 83% of G8-10, while rejecting 98% of controls. Conclusion: In this study, we have developed a novel, blood-based biomarker panel which can be used as the basis of a simple blood test to identify men with aggressive prostate cancer and thereby reduce the overdiagnosis and overtreatment that currently results from diagnosis using PSA alone. We discuss possible clinical uses of the panel to identify men more likely to benefit from biopsy and immediate therapy versus those more suited to an "active surveillance" strategy.

AB - Purpose: Prostate cancer is a bimodal disease with aggressive and indolent forms. Current prostate-specific-antigen testing and digital rectal examination screening provide ambiguous results leading to both under-and over-treatment. Accurate, consistent diagnosis is crucial to risk-stratify patients and facilitate clinical decision making as to treatment versus active surveillance. Diagnosis is currently achieved by needle biopsy, a painful procedure. Thus, there is a clinical need for a minimally-invasive test to determine prostate cancer aggressiveness. A blood sample to predict Gleason score, which is known to reflect aggressiveness of the cancer, could serve as such a test. Materials and Methods: Blood mRNA was isolated from North American and Malaysian prostate cancer patients/controls. Microarray analysis was conducted utilizing the Affymetrix U133 plus 2·0 platform. Expression profiles from 255 patients/controls generated 85 candidate biomarkers. Following quantitative real-time PCR (qRT-PCR) analysis, ten disease-associated biomarkers remained for paired statistical analysis and normalization. Results: Microarray analysis was conducted to identify 85 genes differentially expressed between aggressive prostate cancer (Gleason score ≥8) and controls. Expression of these genes was qRT-PCR verified. Statistical analysis yielded a final seven-gene panel evaluated as six gene-ratio duplexes. This molecular signature predicted as aggressive (ie, Gleason score ≥8) 55% of G6 samples, 49% of G7(3+4), 79% of G7(4+3) and 83% of G8-10, while rejecting 98% of controls. Conclusion: In this study, we have developed a novel, blood-based biomarker panel which can be used as the basis of a simple blood test to identify men with aggressive prostate cancer and thereby reduce the overdiagnosis and overtreatment that currently results from diagnosis using PSA alone. We discuss possible clinical uses of the panel to identify men more likely to benefit from biopsy and immediate therapy versus those more suited to an "active surveillance" strategy.

UR - http://www.scopus.com/inward/record.url?scp=84867028271&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84867028271&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0045802

DO - 10.1371/journal.pone.0045802

M3 - Article

C2 - 23071848

AN - SCOPUS:84867028271

VL - 7

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 9

M1 - e45802

ER -