Prostate cancer (PCa) is the second leading cause of cancer-related death among men. Prostate-specific antigen (PSA) testing is used in screening programs for early detection with a consequent reduction of PCa-specific mortality at the cost of overdiagnosis and overtreatment of the nonaggressive PCa. Recently, several assays have been commercially developed to implement PCa diagnosis, but they have not been included in both screening and diagnosis of PCa. This review aims to describe the actual and novel commercially available molecular biomarkers that can be used in PCa management to implement and tailor the screening and diagnosis of PCa.
Humans ; Prostatic Neoplasms/genetics* ; Male ; Biomarkers, Tumor/genetics* ; Early Detection of Cancer/methods* ; Prostate-Specific Antigen/blood* ; Molecular Diagnostic Techniques/methods* ; Glutamate Carboxypeptidase II/metabolism*

Prostate cancer is one of the most common malignant tumors in men and posing a serious threat to men's health. Detection methods such as prostate-specific antigen (PSA), prostate biopsy, and magnetic resonance imaging are widely used for prostate cancer screening, but they have low specificity, high cost, and significant risks. Therefore, there is an urgent need to develop highly specific, low-cost, easily obtained, stable, and reliable biomarkers, and use them as the basis to establish non-invasive screening and diagnostic methods for prostate cancer. This paper reviewed the recent advances in the use of prostate cancer biomarkers and combined detection methods for prostate cancer diagnosis and prognosis assessment and provides an in-depth analysis and comparison of different biomarkers and combined detection methods, as well as points out the directions and challenges for future research. The paper emphasizes the importance of developing efficient, cost-effective and easy-to-implement biomarkers to increase the early diagnosis rate of prostate cancer, improve patient prognosis, and reduce the waste of healthcare resources. This paper provides an important theoretical basis and technical guidance for early diagnosis, precise treatment and prognostic evaluation of prostate cancer, and has important reference value for promoting clinical research and practice of prostate cancer.
Humans ; Male ; Prostatic Neoplasms/diagnosis* ; Biomarkers, Tumor/blood* ; Early Detection of Cancer/methods* ; Prognosis ; Prostate-Specific Antigen/blood* ; Glutamate Carboxypeptidase II/metabolism* ; Antigens, Neoplasm/blood* ; Antigens, Surface ; Serine Endopeptidases

Objective: To investigate the safety and effectiveness of radical retropubic prostatectomy (RRP) with adjuvant androgen deprivation or external radiotherapy in the treatment of prostate cancer (PCa) with pelvic lymph node metastasis (PLNM). METHODS: Twenty PCa patients underwent bilateral pedal lymphangiography (PLG) preoperatively, and 11 of them received lymph node aspiration for examination of the mRNA expressions of prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) in the lymph fluid by real-time RT-PCR. All the patients were treated by RRP with extended dissection of pelvic lymph nodes, and 3 of them by external radiotherapy in addition after recovery from urinary incontinence because of positive surgical margins, followed by adjuvant androgen deprivation therapy. RESULTS: Real-time RT-PCR showed positive mRNA expressions of PSA and PSMA in the lymph fluid of the 11 patients, all pathologically confirmed with PLNM. The median intraoperative blood loss was 575 ml, with blood transfusion for 5 cases. Positive surgical margin was found in 3 cases, lymphorrhagia in 2 and urinary leakage in another 2 each. There were no such severe complications as vascular injury and rectum perforation. The patients were followed up for 6－48 (mean 42) months, during which, biochemical recurrence was observed in 12 cases at a median of 12 months postoperatively and 2 patients died at 12 and 48 months respectively. CONCLUSIONS Bilateral PLG and lymph node aspiration for examination of the mRNA expressions of PSA and PSMA in the lymph fluid help to confirm PLNM preoperatively. Radical retropubic prostatectomy with adjuvant androgen deprivation or external radiotherapy is safe and effective for the treatment of PCa with PLNM, but it should be chosen cautiously for those with Gleason 5+5.
Androgen Antagonists ; therapeutic use ; Antigens, Surface ; metabolism ; Chemotherapy, Adjuvant ; Glutamate Carboxypeptidase II ; metabolism ; Humans ; Lymph Node Excision ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Male ; Pelvis ; Postoperative Period ; Prostate-Specific Antigen ; metabolism ; Prostatectomy ; methods ; Prostatic Neoplasms ; drug therapy ; metabolism ; surgery

BACKGROUNDProstate specific membrane antigen (PSMA) can facilitate the growth, migration, and invasion of the LNCaP prostate cancer cell lines, but the underlying molecular mechanisms have not yet been clearly defined. Here, we investigated whether PSMA serves as a novel regulator of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling by employing PSMA knockdown model and PI3K pharmacological inhibitor (LY294002) in LNCaP prostate cancer cells.

METHODSPSMA knockdown had been stably established by transfecting with lentivirus-mediated siRNA in our previous study. Then, LNCaP cells were divided into interference, non-interference, and blank groups. We first testified the efficacy of PSMA knockdown in our LNCaP cell line. Then, we compared the expression of PSMA and total/activated Akt by Western blotting in the above three groups with or without LY294002 treatment. Furthermore, immunocytochemistry was performed to confirm the changes of activated Akt (p-Akt, Ser473) in groups. Besides, cell proliferation, migration, and cell cycle were measured by CCK-8 assay, Transwell analysis, and Flow cytometry respectively.

RESULTSAfter PSMA knockdown, the level of p-Akt (Ser473) but not of total-Akt (Akt1/2) was significantly decreased when compared with the non-interference and blank groups. However, LY294002 administration significantly reduced the expression of p-Akt (Ser473) in all the three groups. The results of immunocytochemistry further confirmed that PSMA knockdown or LY294002 treatment was associated with p-Akt (Ser473) down-regulation. Decrease of cell proliferation, migration, and survival were also observed upon PSMA knockdown and LY294002 treatment.

CONCLUSIONSTaken together, our results reveal that PI3K/Akt signaling pathway inhibition may serve as a novel molecular mechanism in LNCaP prostate cancer cells of PSMA knockdown and suggest that Akt (Ser473) may play a critical role as a downstream signaling target effector of PSMA in this cellular model.

Antigens, Surface ; genetics ; metabolism ; Cell Line, Tumor ; Glutamate Carboxypeptidase II ; genetics ; metabolism ; Humans ; Male ; Phosphatidylinositol 3-Kinases ; metabolism ; Prostatic Neoplasms ; enzymology ; genetics ; therapy ; Proto-Oncogene Proteins c-akt ; metabolism ; RNA Interference ; Signal Transduction ; genetics ; physiology

Antigens, Neoplasm ; metabolism ; Antigens, Surface ; metabolism ; Autoantibodies ; metabolism ; Biomarkers, Tumor ; metabolism ; Carrier Proteins ; metabolism ; Glutamate Carboxypeptidase II ; metabolism ; Humans ; Kallikreins ; metabolism ; Male ; MicroRNAs ; metabolism ; Oncogene Proteins, Fusion ; metabolism ; PTEN Phosphohydrolase ; metabolism ; Prostate-Specific Antigen ; metabolism ; Prostatic Neoplasms ; metabolism ; Receptor, Epidermal Growth Factor ; metabolism ; Trypsin Inhibitor, Kazal Pancreatic ; Urokinase-Type Plasminogen Activator ; metabolism

OBJECTIVETo explore the transgenic efficiency of non-viral vector Tf-PEG-PEI and the cell specific silencing effect of plasmid pPSMAe/p-shNS-ploy(A) on prostate cancer cells.

METHODSPolyethyleneimine (PEI) was modified by using polyethylene glycol and transferrin to synthesize the non-viral vector Tf-PEG-PEI. NS-specific plasmids pPSMAe/p-shNS-ploy(A) and Tf-PEG-PEI were used to transfect prostate cancer LNCap and PC-3 cells. The changes of cell morphology, proliferation ability and cell cycle were studied after down-regulating the NS gene level.

RESULTSTf-PEG-PEI was successfully modified. After transfection, the PSMA-expressing LNCaP cells became larger and showed more pseudopodia, having a tendency to differentiate. Their cell proliferation ability was reduced, and the detection of cell cycle showed a decrease of S phase and an increase of G(1) phase after knocking down NS gene. These targets were not changed in non-PSMA-expresing PC-3 cells.

CONCLUSIONSThe non-viral vector Tf-PEG-PEI has a high ability to transfer targeted gene into target cells. The cellular specificity of short-hairpin RNA transcription driven by PSMAe/p is confirmed by silencing NS gene. The use of cell specific promoter may be an effective strategy of gene therapy for prostate cancer.

Antigens, Surface ; genetics ; metabolism ; Cell Cycle ; Cell Line, Tumor ; Cell Proliferation ; GTP-Binding Proteins ; genetics ; metabolism ; Genetic Vectors ; Glutamate Carboxypeptidase II ; genetics ; metabolism ; Humans ; Male ; Nuclear Proteins ; genetics ; metabolism ; Plasmids ; Polyethylene Glycols ; Polyethyleneimine ; analogs & derivatives ; Promoter Regions, Genetic ; Prostatic Neoplasms ; pathology ; RNA Interference ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; genetics ; Transfection ; Transferrin ; genetics

Prostate-specific membrane antigen (PSMA), the research of which has flourished in recent years, is a specific prostate cancer marker. PSMA plays a more and more important role in the early diagnosis, gene treatment and prognosis of the disease course of prostate cancer. This review focuses on the progress in researches of the structure, function, expression traits and gene expression of the PSMA protein, prostate cancer radioimmunoimaging, DNA vaccines and suicide gene therapy based on PSMA, as well as the role of PSMA in the clinical diagnosis and treatment of prostate cancer.
Antigens, Surface ; genetics ; Gene Expression Regulation, Neoplastic ; Glutamate Carboxypeptidase II ; genetics ; Humans ; Male ; Prostate-Specific Antigen ; genetics ; Prostatic Neoplasms ; diagnosis ; genetics ; therapy ; RNA, Messenger ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction

Antigens, Surface ; blood ; Diagnosis, Differential ; Glutamate Carboxypeptidase II ; blood ; Humans ; Male ; Neoplasm Staging ; Prostate-Specific Antigen ; blood ; Prostatic Hyperplasia ; pathology ; Prostatic Neoplasms ; etiology ; metabolism ; pathology ; Racemases and Epimerases ; analysis

OBJECTIVETo study the correlation of prostate-specific membrane antigen (PSMA) and prostate-specific antigen (PSA) expression with Gleason score of prostate carcinoma.

METHODSMonoclonal antibodies against epitopes of PSMA extracellular domain were prepared, with which the expression of PSMA of prostate carcinoma (PC) was determined by immunohistochemical staining. Correlation of its expression with Gleason score of PC was statistically analyzed, and compared with that of PSA.

RESULTSEight hybridoma cell lines secreting monoclonal antibodies specific for PSMA were prepared. PSMA expression level was positively correlated with Gleason score. In poorly differentiated prostate carcinoma, the expression intensity of PSMA was higher than that of medium-and well-differentiated prostate carcinoma (P < 0.01). However, there was no correlation between level of PSA expression and Gleason score (P > 0.05).

CONCLUSIONPSMA expression level may be used as a useful surrogate marker in Gleason grading of prostate carcinoma. It may be a more suitable target than PSA in antibody mediated immunotherapy against poorly differentiated prostate carcinoma which is usually not sensitive to hormonal therapy.

Antigens, Surface ; metabolism ; Biomarkers, Tumor ; metabolism ; Glutamate Carboxypeptidase II ; metabolism ; Humans ; Male ; Prostate-Specific Antigen ; metabolism ; Prostatic Neoplasms ; metabolism ; pathology