Blood-based biomarkers of aggressive prostate cancer.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Lam Wah Ee Hospital, Georgetown, Penang, Malaysia.
Men Long
ML
Liong
Chun Ren
CR
Lim
Hengxuan
H
Yang
Samuel
S
Chao
Chin Wei
CW
Bong
Wing Seng
WS
Leong
Prashanta Kumar
PK
Das
Chit Sin
CS
Loh
Ban Eng
BE
Lau
Choon Geok
CG
Yu
Edie Jian Jiek
EJ
Ooi
Robert K
RK
Nam
Paul D
PD
Allen
Graeme S
GS
Steele
Karl
K
Wassmann
Jerome P
JP
Richie
Choong Chin
CC
Liew
D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D020869:Gene Expression Profiling; D006801:Humans; D016015:Logistic Models; D008296:Malaysia; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D060787:Neoplasm Grading; D009656:North America; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis*; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction
D014408:Biomarkers, Tumor