Quantitative analysis of a panel of gene expression in prostate cancer--with emphasis on NPY expression analysis.
OBJECTIVE
To investigate molecular alterations associating with prostate carcinoma progression and potentially provide information toward more accurate prognosis/diagnosis.


METHODS
A set of laser captured microdissected (LCM) specimens from 300 prostate cancer (PCa) patients undergoing radical prostatectomy (RP) were defined. Ten patients representing "aggressive" PCa, and 10 representing "non-aggressive" PCa were selected based on prostate-specific antigen (PSA) recurrence, Gleason score, pathological stage and tumor cell differentiation, with matched patient age and race between the two groups. Normal and neoplastic prostate epithelial cells were collected with LCM from frozen tissue slides obtained from the RP specimens. The expressions of a panel of genes, including NPY, PTEN, AR, AMACR, DD3, and GSTP1, were measured by quantitative real-time RT-PCR (TaqMan), and correlation was analyzed with clinicopathological features.


RESULTS
The expressions of AMACR and DD3 were consistently up-regulated in cancer cells compared to benign prostate epithelial cells in all PCa patients, whereas GSTP1 expression was down regulated in each patient. NPY, PTEN and AR exhibited a striking difference in their expression patterns between aggressive and non-aggressive PCas (P=0.0203, 0.0284, and 0.0378, respectively, Wilcoxon rank sum test). The lower expression of NPY showed association with "aggressive" PCas based on a larger PCa patient cohort analysis (P=0.0037, univariate generalized linear model (GLM) analysis).


CONCLUSIONS
Despite widely noted heterogeneous nature of PCa, gene expression alterations of AMACR, DD3, and GSTP1 in LCM-derived PCa epithelial cells suggest for common underlying mechanisms in the initiation of PCa. Lower NPY expression level is significantly associated with more aggressive clinical behavior of PCa; PTEN and AR may have potential in defining PCa with aggressive clinical behavior. Studies along these lines have potential to define PCa-associated gene expression alterations and likely co-regulation of genes/pathways critical in the biology of PCa onset/progression.
Liu
Ai-jun
AJ
Department of Pathology, Chinese PLA General Hospital, Beijing 100853, China. aliu301@yahoo.com.cn
Furusato
Bungo
B
Ravindranath
Lakshmi
L
Chen
Yong-mei
YM
Srikantan
Vasanta
V
McLeod
David G
DG
Petrovics
Gyorgy
G
Srivastava
Shiv
S
D000951:Antigens, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D051549:Glutathione S-Transferase pi / Q000235:genetics; D006801:Humans; D008297:Male; D009478:Neuropeptide Y / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D019998:Racemases and Epimerases / Q000235:genetics; D011944:Receptors, Androgen / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D013997:Time Factors
D000951:Antigens, Neoplasm; D009478:Neuropeptide Y; D012333:RNA, Messenger; D011944:Receptors, Androgen; C479341:prostate cancer antigen 3, human; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D019998:Racemases and Epimerases; C108352:alpha-methylacyl-CoA racemase