Allelic loss of the loci containing the androgen synthesis gene, StAR, is prognostic for relapse in intermediate-risk prostate cancer.
BACKGROUND
Androgen deprivation therapy (ADT) and novel agents targeting the androgen synthesis axis (e.g., abiraterone acetate) are adjuvant therapies that are currently, or may in the future be, combined with radiotherapy to reduce the chance of disease relapse. Little is known about allelic loss or gain pertaining to genes associated with the androgen synthesis axis and whether this is prognostic in patients who receive localized radiotherapy. In this hypothesis generating study, we conducted an array comparative genomic hybridization (aCGH) analysis of 33 androgen synthesis genes to identify potential prognostic factors for radiotherapy outcome.


METHODS
aCGH analysis of tumor DNA prospectively derived from frozen needle biopsies of 126 men with intermediate-risk disease who underwent image-guided radiotherapy (IGRT) to a mean dose of 76.4 Gy was conducted. Statistical analyses were conducted for allelic loss or gain in genes as potential prognostic factors relative to prostate specific antigen, Gleason-score, and T-category.


RESULTS
We observed that allelic losses of loci containing the genes StAR and HSD17B2 were associated with increased genetic instability (as determined by percentage genome alteration). On multivariate analyses these loci were prognostic for biochemical disease-free relapse (StAR: HR = 2.84, 95% CI: 1.44-5.61, P = 0.00269; HSD17B2: HR = 1.97, 95% CI: 1.06-3.64, P = 0.031). The results were validated in a surgical cohort of 131 intermediate-risk patients.


CONCLUSIONS
Allelic losses of the loci containing StAR and HSD17B2 have significant prognostic value for intermediate-risk prostate cancer. With this hypothesis generating information future studies should test StAR and HSD17B2 losses as biomarkers of androgen response in combined modality protocols.
Department of Radiation Oncology, Medical Biophysics, Laboratory Medicine and Pathology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
Jennifer A
JA
Locke
Gaetano
G
Zafarana
Chad A
CA
Malloff
Wan L
WL
Lam
Jenna
J
Sykes
Melania
M
Pintilie
Varune Rohan
VR
Ramnarine
Alice
A
Meng
Omer
O
Ahmed
Igor
I
Jurisica
Emma Tomlinson
ET
Guns
Theo
T
van der Kwast
Michael
M
Milosevic
Robert G
RG
Bristow
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D000728:Androgens / Q000096:biosynthesis* / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics; D015331:Cohort Studies; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D012307:Risk Factors; D000098682:Steroidogenic Acute Regulatory Protein
D000728:Androgens; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein