DNA methylation is a common event in malignancies and implicated in tumor initiation and progression. There is a battery of genes involved in critical cell processes such as DNA damage repair, which are hypermethylated in prostate cancer. DNA methylation has also been found in premalignant lesions such as prostatic intraepithelial neoplasia, but to a less extent compared with that in prostate cancer. Intensive study on DNA methylation would provide a new opportunity for the early diagnosis, prognosis and treatment of prostate cancer.
DNA Methylation ; Humans ; Male ; Prognosis ; Prostatic Neoplasms ; diagnosis ; genetics

OBJECTIVETo screen methylations of CpG islands in prostate cancer using restriction landmark genomic scanning (RLGS).

METHODSThe DNA was extracted from homogeneous cells captured by laser capture microdissection in 20 prostate cancer and 18 benign prostatic hyperplasia (BPH) tissues for scanning the CpG islands using RLGS. The methylation status of each CpG island was compared between the cancer and BPH samples to screen the genes involved in prostate cancer development. The screened genes were uploaded to DAVID database for GO analysis, and the genes with the most significant methylation were analyzed by pyrosequencing.

RESULTS AND CONCLUSIONAmong all the tested CpG islands, 10245 (37.2%) in prostate cancer and 8658 (30.3%) in BPH samples were found to be abnormally methylated, and >60% of the methylated CpG islands were in the promoter region. Compared with BPH samples, the prostate cancer samples showed differential methyation in 735 CpG islands, including 458 hepermethyated and 256 hypomethelated ones. Seven genes (DPYS, P16, APC, GSTP1, TMEM122, RARB, and ARHGAP20) in prostate cancer were identified to have distinct methylations. Bioinformatics analysis suggested that these genes were associated with several biomolecular and biological processes, and among them DPYS gene was involved in 13 GO anotated biologic functions, development of 50 diseases and 47 protein interactions. Pyrosequencing of 7 sites of the CPG island in DPYS gene showed a methylation frequency of 32.7%, suggesting the importance of DPYS gene in the carcinogenesis and progression of prostate cancer.

CpG Islands ; DNA Methylation ; DNA, Neoplasm ; genetics ; Genomics ; Humans ; Male ; Polymerase Chain Reaction ; Prostatic Hyperplasia ; genetics ; Prostatic Neoplasms ; diagnosis ; genetics

RASSF1A gene cloned from 3p21.3 region is a novel candidate tumor suppressor gene. The aberrant methylation of CpG lands in the promoter region is the major inactivation mechanism of RASSF1A, and is significantly involved in the genesis and development of multiple solid tumors including prostate cancer. The methylation status examination of RASSF1A could serve as an important technique for the early diagnosis of prostate cancer, while methylation inhibitor is likely to become a novel therapeutic agent.
DNA Methylation ; Early Diagnosis ; Humans ; Male ; Prostatic Neoplasms ; diagnosis ; genetics ; Tumor Suppressor Proteins ; genetics

There is evidence that a substantial part of genetic predisposition to prostate cancer (PCa) may be due to lower penetrance genes which are found by genome-wide association studies. We have recently conducted such a study and seven new regions of the genome linked to PCa risk have been identified. Three of these loci contain candidate susceptibility genes: MSMB, LMTK2 and KLK2/3. The MSMB and KLK2/3 genes may be useful for PCa screening, and the LMTK2 gene might provide a potential therapeutic target. Together with results from other groups, there are now 23 germline genetic variants which have been reported. These results have the potential to be developed into a genetic test. However, we consider that marketing of tests to the public is premature, as PCa risk can not be evaluated fully at this stage and the appropriate screening protocols need to be developed. Follow-up validation studies, as well as studies to explore the psychological implications of genetic profile testing, will be vital prior to roll out into healthcare.
Genetic Predisposition to Disease ; genetics ; Genetic Testing ; Humans ; Kallikreins ; genetics ; Male ; Membrane Proteins ; genetics ; Prostatic Neoplasms ; diagnosis ; genetics ; Prostatic Secretory Proteins ; genetics ; Protein-Serine-Threonine Kinases ; genetics ; Risk Factors

Prostate cancer ( PCa) is an important genitourinary malignancy with increasing morbidity and mortality. Glutathione S-transferase P1 ( GSTP1) , as a phrase- II enzyme, has an important role in the activation and detoxification of carcinogens. There is a close association between GSTP1 gene polymorphisms and the risk of Pca. GSTP1 CpG island hypermethylation can reliably distinguish Pca from benign prostatic hyperplasia( BPH) and promises to be an important molecular marker for the diagnosis of Pca. This paper summarizes the association of GSTP1 with the diagnosis and risk of Pca.
Glutathione S-Transferase pi ; genetics ; Humans ; Male ; Prostatic Neoplasms ; diagnosis ; etiology

OBJECTIVETo investigate the relationship between six-transmembrane epithelial antigen of the prostate (STEAP) expression and the histologic grading of prostatic carcinoma (PCa).

METHODSDifferent prostatic tissues and non-prostatic tumors, 131 cases of PCa, 164 cases of benign prostate hyperplasia (BPH), and 56 cases of non-prostatic malignancies, were analyzed for the expression of STEAP by using STEAP monoclonal antibody and SP immunohistochemical staining. The positive area unit (PU) was introduced to describe the intensity of STEAP expression.

RESULTSThe prostatic tissues of all but 3 cases of PCa and 5 cases of BPH were stained positively, while all of the non-prostatic tumors were stained negatively. There was a significant negative correlation between the STEAP expression and the histologic grading of PCa.

CONCLUSIONSTEAP can be a prognostic marker of PCa and a potential therapeutic target in PCa.

Antigens, Neoplasm ; analysis ; genetics ; Humans ; Immunohistochemistry ; Male ; Oxidoreductases ; Prostatic Neoplasms ; diagnosis ; immunology ; pathology

Prostate stem cell antigen (PSCA) is a cell surface antigen expressed in normal prostate and overexpressed in cancers associated with prostate, bladder and pancreas. The sensitivity of PSCA labeling is higher than PSA in prostate cancer. PSCA can be used in the preparation of protein vaccine and nucleic acid vaccine. Further studies are required to confirm its safety and efficacy as a diagnostic means.
Antigens, Neoplasm ; GPI-Linked Proteins ; Humans ; Immunotherapy ; Male ; Membrane Glycoproteins ; analysis ; genetics ; immunology ; Neoplasm Proteins ; analysis ; genetics ; immunology ; Pancreatic Neoplasms ; diagnosis ; Prostatic Neoplasms ; diagnosis ; Urinary Bladder Neoplasms ; diagnosis

BACKGROUNDEarly diagnosis and timely treatment are important for improving therapeutic efficiency of prostate cancer. DNA array is a new bio-technology for disease diagnosis. This study was conducted to diagnose prostate cancer with cDNA macroarray and analysis gene expression profiles of some selective genes in prostate cancer.

METHODSTotal RNA was isolated from patients with prostate cancer and from normal people, and poly (A) RNA was further purified. Then it was analyzed for differentially expressed genes in prostate cancer and normal prostate by cDNA macroarray system.

RESULTSThere were different expressions in the nine prostate-associated specific genes in prostate cancer as compared with normal prostate, in which, 7 were significantly upregulated and 2 were down-regulated.

CONCLUSIONAs a diagnostic approach at molecular level, the cDNA macroarray is an effectively diagnostic method for prostate cancer.

Gene Expression Profiling ; Genes, Tumor Suppressor ; Humans ; Male ; Oligonucleotide Array Sequence Analysis ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms ; diagnosis ; genetics

The potential use of urinary nucleic acids as diagnostic markers in prostate cancer (PCa) was evaluated. Ninety-five urine samples and 234 prostate tissue samples from patients with PCa and benign prostatic hyperplasia (BPH) were analyzed. Micro-array analysis was used to identify candidate genes, which were verified by the two-gene expression ratio and validated in tissue mRNA and urinary nucleic acid cohorts. Real-time quantitative polymerase chain reaction (qPCR) was used to measure urinary nucleic acid levels and tissue mRNA expression. The TSPAN13-to-S100A9 ratio was selected to determine the diagnostic value of urinary nucleic acids in PCa (P = 0.037) and shown to be significantly higher in PCa than in BPH in the mRNA and nucleic acid cohort analyses (P < 0.001 and P = 0.013, respectively). Receiver operating characteristic (ROC) analysis showed that the area under the ROC curve was 0.898 and 0.676 in tissue mRNA cohort and urinary nucleic acid cohort, respectively. The TSPAN13-to-S100A9 ratio showed a strong potential as a diagnostic marker for PCa. The present results suggest that the analysis of urine supernatant can be used as a simple diagnostic method for PCa that can be adapted to the clinical setting in the future.
Aged ; Aged, 80 and over ; Biomarkers, Tumor/*genetics/*urine ; Calgranulin B/*genetics ; Cohort Studies ; Humans ; Male ; Middle Aged ; Nucleic Acids/*genetics/*urine ; Oligonucleotide Array Sequence Analysis ; Prostate/metabolism ; Prostatic Hyperplasia/diagnosis/genetics/urine ; Prostatic Neoplasms/diagnosis/*genetics/*urine ; RNA, Messenger/genetics/metabolism ; RNA, Neoplasm/genetics/metabolism ; ROC Curve ; Real-Time Polymerase Chain Reaction ; Tetraspanins/*genetics

Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Leukemia, Myeloid, Chronic-Phase ; genetics ; Lymphoma ; classification ; diagnosis ; pathology ; Male ; Neoplasms ; genetics ; metabolism ; pathology ; Oncogene Proteins ; metabolism ; Prognosis ; Prostatic Neoplasms ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Translocation, Genetic ; Tumor Suppressor Proteins ; metabolism