Identification of prognostic biomarkers for prostate cancer.
OBJECTIVE
This paper describes a process for the identification of genes that can report on the aggressiveness of prostate tumors and thereby add to the information provided by current pathologic analysis.


METHODS
Expression profiling data from over 100 laser capture microdissection derived samples from nonneoplastic epithelium; Gleason patterns 3, 4, and 5 and node metastasis prostate cancer were used to identify genes at abnormally high levels in only some tumors. These variably overexpressed genes were stratified by their association with aggressive phenotypes and were subsequently filtered to exclude genes with redundant expression patterns. Selected genes were validated in a case-control study in which cases (systemic progression within 5 years) and controls (no systemic progression at 7 years of follow-up) were matched for all clinical and pathologic criteria from time of prostatectomy (n = 175). Both cases and controls, therefore, could have nodal invasion or seminal vesicle involvement at the time of initial treatment.


RESULTS
A number of candidate variably overexpressed genes selected for their association with aggressive prostate cancer phenotype were evaluated in the case control study. The most prominent candidates were SSTR1 and genes related to proliferation, including TOP2A.


CONCLUSIONS
The process described here identified genes that add information not available from current clinical measures and can improve the prognosis of prostate cancer.
Kosari
Farhad
F
Mayo Clinic Cancer Center, Department of Laboratory Medicine and Pathology, Rochester, Minnesota 55905, USA.
Munz
Jan Marie A
JM
Savci-Heijink
C Dilara
CD
Spiro
Craig
C
Klee
Eric W
EW
Kube
Dagmar Marie
DM
Tillmans
Lori
L
Slezak
Jeff
J
Karnes
R Jeffrey
RJ
Cheville
John C
JC
Vasmatzis
George
G
D000951:Antigens, Neoplasm / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000302:isolation & purification; D016022:Case-Control Studies; D016000:Cluster Analysis; D004250:DNA Topoisomerases, Type II / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D001330:Electronic Data Processing; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D000075223:Poly-ADP-Ribose Binding Proteins; D011379:Prognosis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D017481:Receptors, Somatostatin / Q000235:genetics
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D017481:Receptors, Somatostatin; C101130:somatostatin receptor type 1; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human