Gene Expression Profiling Of Human Prostate Cancer And Benign Prostatic Hyperplasia Originated From The Peripheral Zone

Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are common benign/malignant prostatic diseases of elder male population. As McNeal's classical concept of zonal anatomy of the prostate, many people believe BPH is originated from the transition zone (i.e. inner gland), while PCa from the peripheral zone (i.e. outer gland). During long-year's prostate biopsy, we found primary BPH could also occur in the peripheral zone, and related articles were reported.Pathogenesis of benign/malignant disease is a complex process involving multi-gene's expression change, including proliferation, differentiation, apoptosis, signal pathway, transcription, and cell structure. Analysis of disease-related genes could deepen the understanding of molecular mechanism of disease, help to make appropriate diagnosis and prognosis. It is also provided theoretical support for gene therapy.Reports and articles of BPH in PZ were rare, and all limited to case report. There has no published report of gene expression profiling of BPH in PZ, and its pathogenesis is unclear so far. In our study, we aimed to analysis gene expression profiling using micrroarray, evaluate molecular change and mechanism of BPH in PZ, and make sure whether BPH could originated from PZ. Furthermore, to speculate possible molecular mechanism of BPH and PCa of PZ; to screen important disease-related gene, and locate their function, for further research provide theoretical support.As the rapid development of molecular biology, researches are becoming focus on new instrument-gene chip, from the DNA, RNA and protein level to reveal the pathogenesis. Human Whole Genome OneArray DNA Microarrays were provided by Phalanx Biotech Group, Inc., it include 30,968 human genome probe and 1082 control probe. The results as follows:1. Normal PZ tissue, BPH in PZ and PCa in PZ were obtained for microarray detection; 555 PCa-related genes were obtained (392 were up-regulated and 163 were down-regulated). Functional classification of different genes as follows: (1) cellular component: intracellular part (cytoplasm, ribosome), organelle, protein complex; (2) molecular function: catalytic activity (lyase activity, oxidoreductase activity, acetyltransferase activity), structural molecule activity, RNA binding; (3) biological process: biosynthesis and metabolism (nitrogen compound, protein, fatty acid, ribonucleotide), cell growth, cellular physiological process (regulation of cell size, cellular localization).2. PCa-related genes has 10 significant related gene pathway (KEGG):Oxidative phosphorylation, Ribosome, Focal adhesion, Tryptophan metabolism, Arginine and proline metabolism, Glycolysis / Gluconeogenesis, Fatty acid metabolism, Cholera-Infection, Propanoate metabolism, Proteasome.3. BPH-related genes were 323, 181 was up-regulated and 142 was down-regulated. Functional classification of different genes as follows: (1) cellular component: cytoplasm, ribosome, protein complex; (2) molecular function: structural molecule activity, transcription factor activity, RNA binding; (3) biological process: macromolecule biosynthesis, protein biosynthesis and chromatin modification.4. BPH-related pathway (KEGG): Ribosome, MAPK signaling pathway, Cell adhesion molecules, Oxidative phosphorylation, Proteasome et al. Ribosome was significant related gene set.5. There was significant difference between BPH and PCa. PCa involved more different genes than BPH; the molecular fundament was obvious different between these two diseases; BPH was still under biological control while abnormal growth of PCa was already out of control.6. FOS and JUN are up-regulated in the BPH tissue of PZ, we speculate BPH of PZ has the potential to transform to the malignancy.7. Ribosomal protein genes have expressed significant both in BPH and PCa, but they up-regulated in PCa group, while down-regulated in BPH group. This may due to their different regulation mechanism. Further investment would help to understand prostatic diseases pathogenesis, and also provide theoretical basement for gene therapy.