Quantitative analysis of a panel of gene expression in prostate cancer—with emphasis on NPY expression analysis

Abstract

Abstract: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). Conclusion: 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.

Neuropeptide Y expression in primary cutaneous melanoma

“…10 The role of NPY in human tumours is unclear. Several studies have indicated the existence of a correlation between NPY and cancer progression in tumours such as neuroblastoma, 11 prostate cancer, 12 non-Hodgkin lymphoma, 13 breast cancer, 14 Ewing sarcoma cells and intracranial tumours. 14 The latter study also demonstrated an association between NPY and decreased tumour growth and differentiation.…”

Neuropeptide Y inhibits cholangiocarcinoma cell growth and invasion

“…In the present study, the diffuse positivity of the neuroendocrine marker, NPY, observed in human ductular cholangiocarcinoma samples is supported by a number of studies. Indeed, Liu et al (33) have demonstrated higher expression of NPY in nonaggressive prostate epithelial tumors. Moreover, these observations about the nonconventional immunolocalization of neuroendocrine proteins are previously discussed in cholestasis and cholangiocarcinoma where the important role of GABA, chromogranin A, glycolipid A2-B4, S-100 protein, and neural cell adhesion molecule are demonstrated by us and other groups (17, 37, 46 -48), suggesting that the biliary epithelium is a significant target for the neuroendocrine system.…”

IL-15 regulates migration, invasion, angiogenesis and genes associated with lipid metabolism and inflammation in prostate cancer

“…In addition to inflammation, differences in gene expression patterns and genome instability are associated with cancer progression [18,19]. In PCa, one of the most studied gene mutations is the loss of phosphatatse and tensin homolog (PTEN).…”