Prostate cancer is one of the most common types of cancer found to occur in males and is ranked as the second-highest cause of cancer-associated deaths among male patients. In this study, we have shown the influence of a new palladium-based anticancer agent in contrast to the six distinct prostate cancer lines and the primary cultures.

The prostate specific antigen (PSA) test is widely used for early diagnosis of prostate cancer (PCa). However, its limited sensitivity has led to over-diagnosis and over-treatment of PCa. Glycosylation alteration is a common phenomenon in cancer development. Different PSA glycan subforms have been proposed as diagnostic markers to better differentiate PCa from benign prostate hyperplasia (BPH). In this study, we purified PSA from expressed prostate secretions (EPS)-urine samples from 32 BPH and 30 PCa patients and provided detailed PSA glycan profiles in Chinese population. We found that most of the PSA glycans from EPS-urine were complex type biantennary glycans. We observed two major patterns in PSA glycan profiles. Overall there was no distinct separation of PSA glycan profiles between BPH and PCa patients. However, we detected a significant increase of glycan FA2 and FM5A2G2S1 in PCa when compared with BPH patients. Furthermore, we observed that the composition of FA2 glycan increased significantly in advanced PCa with Gleason score ≥8, which potentially could be translated to clinic as a marker for aggressive PCa.

Genome-wide association studies (GWASs) of prostate cancer have identified >250 significant risk loci, but the causal variants and mechanisms for these loci remain largely unknown. Here, we sought to identify and characterize risk-harboring regulatory elements by integrating epigenomes from primary prostate tumor and normal tissues of 27 individuals across the H3K27ac, H3K4me3, and H3K4me2 histone marks and FOXA1 and HOXB13 transcription factors. We identified 7,371 peaks with significant allele specificity (allele-specific quantitative trait locus [asQTL] peaks). Showcasing their relevance to prostate cancer risk, H3K27ac T-asQTL peaks were the single annotation most enriched for prostate cancer GWAS heritability (40×), significantly higher than corresponding non-asQTL H3K27ac peaks (14×) or coding regions (14×). Surprisingly, fine-mapped GWAS risk variants were most significantly enriched for asQTL peaks observed in tumors, including asQTL peaks that were differentially imbalanced with respect to tumor-normal states. These data pinpointed putative causal regulatory elements at 20 GWAS loci, of which 11 were detected only in the tumor samples. More broadly, tumor-specific asQTLs were enriched for expression QTLs in benign tissues as well as accessible regions found in stem cells, supporting a hypothesis where some germline variants become reactivated during or after transformation and can be captured by epigenomic profiling of the tumor. Our study demonstrates the power of allele specificity in chromatin signals to uncover GWAS mechanisms, highlights the relevance of tumor-specific regulation in the context of cancer risk, and prioritizes multiple loci for experimental follow-up.

Chronic inflammation is frequently observed on histological analysis of malignant and non-malignant prostate specimens. It is a suspected supporting factor for prostate diseases and their progression and a main cause of false positive PSA tests in cancer screening. We hypothesized that inflammation induces autoantibodies, which may be useful biomarkers. We aimed to identify and validate prostate inflammation associated serum autoantibodies in prostate cancer patients and evaluate the expression of corresponding autoantigens.

Objective  The current study was undertaken to investigate the utility of total prostate-specific antigen (tPSA), its isoform [-2] proPSA (p2PSA), and prostate health index (PHI) in the diagnosis of metastatic prostate cancer (PCa). Materials and Methods  This study was conducted from March 2016 to May 2019. Eighty-five subjects who were diagnosed with PCa for the first time, following transrectal ultrasound-guided prostate biopsy, were included in the study. The prebiopsy blood samples were analyzed in Beckman Coulter Access-2 Immunoanalyzer for tPSA, p2PSA, and free PSA (fPSA), and the calculated parameters included %p2PSA, %fPSA, and PHI. Mann-Whitney's U test was used as test of significance, and p -value less than 0.05 was considered statistically significant. Results  Of the 85 participants, 81.2% ( n  = 69) had evidence of metastasis, both clinically and pathologically. The median tPSA (ng/mL), p2PSA (pg/mL), %p2PSA, and PHI were significantly higher in the group with evidence of metastasis (46.5 vs. 13.76; 198.0 vs. 35.72; 3.25 vs. 1.51; 237.58 vs. 59.74, respectively). The sensitivity (%), specificity (%), negative predictive value (%), and positive predictive value (%) to diagnose metastatic PCa of tPSA at a cutoff of 20 ng/mL, PHI at a cutoff of 55, and %p2PSA at a cutoff of 1.66 were 92.7, 98.5, and 94.2; 37.5, 43.7, and 62.5; 54.5, 87.5, and 71.4; and 86.4, 88.3, and 91.5, respectively. Conclusion  Using tests such as %p2PSA and PHI in the standard armamentarium for the diagnosis of metastatic PCa in addition to PSA will help in selecting the appropriate treatment strategy, including active surveillance.

Prostate cancer is the second commonest cancer in men worldwide. At present, every patient with lower urinary tract symptoms (LUTS) in St. Mary's Hospital Lacor is undergoing prostate biopsy regardless of the prostate specific antigen (PSA) level. We sought to determine the association between PSA and malignant prostate histology.

Financial toxicity (FT) is a growing concern among cancer survivors that adversely affects the quality of life and survival. Individuals diagnosed with aggressive cancers are often at a greater risk of experiencing FT. The objectives of this study were to estimate FT among prostate cancer (PCa) survivors after 10-15 years of diagnosis, assess the relationship between PCa aggressiveness at diagnosis and FT, and examine whether current cancer treatment status mediates the relationship between PCa aggressiveness and FT.

Prostate fibroblasts promote prostate cancer progression by secreting factors that enhance tumour growth and induce the migration and invasion of prostate cancer cells. Considering the role of fibroblasts in cancer progression, we hypothesized that prostate cancer cells recruit these cells to their vicinity, where they are most directly available to influence cancer cell behaviour. To test this hypothesis, we performed modified Boyden chamber assays assessing the migration and collagen I invasion of normal primary prostate fibroblasts (PrSCs) and prostate cancer-associated fibroblasts (PCAFs) in response to media conditioned by the metastatic prostate cancer cell lines PC-3, LNCaP and DU145. During 4-hr incubations, PrSCs and PCAFs migrated and invaded in response to the conditioned media. To identify candidate proteins in the conditioned media that produced these effects, we performed cytokine antibody arrays and detected angiogenin in all three media. Angiogenin-blocked PC-3-conditioned medium, obtained using an anti-angiogenin polyclonal antibody or angiogenin siRNA, significantly reduced PC-3-induced PrSC and PCAF collagen I invasion. Furthermore, angiogenin alone at 1, 2 and 5 ng/ml significantly stimulated PCAF collagen I invasion. These results suggest that PC-3-derived angiogenin stimulates the invasion of normal prostate fibroblasts and PCAFs and is sufficient for invasion of the latter. Because prostate fibroblasts play key roles in prostate cancer progression, targeting their invasion using an anti-angiogenin-based therapy may be a strategy for preventing or treating advanced prostate cancer.

To explore the microbiome of the prostatic fluid in high prostate-specific antigen (PSA) patients.

Transcriptomic landscape of prostate cancer (PCa) shows multidimensional variability, potentially arising from the cell-of-origin, reflected in serum markers, and most importantly related to drug sensitivities. For example, Aggressive Variant Prostate Cancer (AVPC) presents low PSA per tumor burden, and characterized by de novo resistance to androgen receptor signaling inhibitors (ARIs). Understanding PCa transcriptomic complexity can provide biological insight and therapeutic guidance. However, unsupervised clustering analysis is hindered by potential confounding factors such as stromal contamination and stress-related material degradation.

Prostate cancer is one of the most common malignancies and the second leading cause of death from cancer in men. The molecular mechanisms driving prostate carcinogenesis are complex; with several lines of evidence suggesting that the reexpression of conserved developmental programs plays a key role. In this study, we used conditional gene targeting and organ grafting, to describe conserved roles for the transcription factor Sox9 in the initiation of both prostate organogenesis and prostate carcinogenesis in murine models. Abrogation of Sox9 expression prior to the initiation of androgen signaling blocks the initiation of prostate development. Similarly, Sox9 deletion in two genetic models of prostate cancer (TRAMP and Hi-Myc) prevented cancer initiation. Expression profiling of Sox9-null prostate epithelial cells revealed that the role of Sox9 in the initiation of prostate development may relate to its regulation of multiple cytokeratins and cell adherence/ polarity. Due to its essential role in cancer initiation, manipulation of Sox9 targets in at-risk men may prove useful in the chemoprevention of prostate cancer.

Seoritae is a type of black soybean that is known to have health-promoting effects due to its high isoflavone and anthocyanin contents. We evaluated whether Seoritae extract (SE) had beneficial effects on the reduction of prostate weight in a rat model of benign prostatic hyperplasia (BPH). BPH was induced by intramuscular injections of testosterone enanthate once a week for 5 weeks in Sprague-Dawley rats, and rats were treated with or without daily oral doses of SE during BPH induction. After 5 weeks, the oxidative stress (superoxide dismutase and 8-hydroxy-2-deoxyguanosine), apoptosis (caspase-3), and activity of 5-alpha reductase were evaluated in the serum and prostate. The SE treatment group showed a significant decrease in prostate weight, oxidative stress, apoptosis, and 5-alpha reductase activity compared to the nontreated BPH group. These results show that SE is effective in decreasing the weight and proliferation of the prostate, and suggest that SE may be an effective treatment for BPH.

Benign prostatic hyperplasia (BPH) is one of the most common diseases in middle-aged and elderly men. In the present study, we aimed to compare the efficacy and safety of thulium laser resection of the prostate (TMLRP) with either transurethral plasmakinetic resection of the prostate (TUPKP) or transurethral resection of the prostate (TURP). A literature search was performed, eventually, 14 studies involving 1587 patients were included. Forest plots were produced by using Revman 5.2.0 software. Our meta-analysis showed that operation time, decrease in hemoglobin level, length of hospital stay, catheterization time, and development of urethral stricture significantly differed, whereas the transitory urge incontinence rate, urinary tract infection rate, and recatheterization rate did not significantly differ between TMLRP and either TURP or TUPKP. The blood transfusion rate was significantly different between TMLRP and TURP, but not between TMLRP and TUPKP. In addition, the retrograde ejaculation rate between TMLRP and TURP did not significantly differ. At 1, 3, 6, and 12 months of postoperative follow-up, the maximum flow rate, post-void residual, quality of life, and International Prostate Symptom Score did not significantly differ among the procedures. Thus, the findings of this study indicate that TMLRP may be a safe and feasible alternative.

Prostate-specific antigen (PSA)-based screening for prostate cancer has been widely performed, but its accuracy is unsatisfactory. To improve accuracy, building an effective statistical model using machine learning methods (MLMs) is a promising approach.

Metastatic tumors that have become resistant to androgen deprivation therapy represent the major challenge in treating prostate cancer. Although these recurrent tumors typically remain dependent on the androgen receptor (AR), non-AR-driven tumors that also emerge are particularly deadly and becoming more prevalent. Here, we present a new genetically engineered mouse model for non-AR-driven prostate cancer that centers on a negative regulator of G protein-coupled receptors that is downregulated in aggressive human prostate tumors. Thus, prostate-specific expression of a dominant-negative G protein-coupled receptor kinase 2 (GRK2-DN) transgene diminishes AR and AR target gene expression in the prostate, and confers resistance to castration-induced involution. Further, the GRK2-DN transgene dramatically accelerates oncogene-initiated prostate tumorigenesis by increasing primary tumor size, potentiating visceral organ metastasis, suppressing AR, and inducing neuroendocrine marker mRNAs. In summary, GRK2 enforces AR-dependence in the prostate, and the loss of GRK2 function in prostate tumors accelerates disease progression toward the deadliest stage.

Polygenic risk scores (PRS) for prostate cancer incidence have been proposed to optimize prostate cancer screening. Prediction of lethal prostate cancer is key to any stratified screening program to avoid excessive overdiagnosis. Herein, PRS for incident prostate cancer was evaluated in two population-based cohorts of unscreened middle-aged men linked to cancer and death registries: the Västerbotten Intervention Project (VIP) and the Malmö Diet and Cancer study (MDC). SNP genotypes were measured by genome-wide SNP genotyping by array followed by imputation or genotyping of selected SNPs using mass spectrometry. The ability of PRS to predict lethal prostate cancer was compared to PSA and a commercialized pre-specified model based on four kallikrein markers. The PRS was associated with incident prostate cancer, replicating previously reported relative risks, and was also associated with prostate cancer death. However, unlike PSA, the PRS did not show stronger association with lethal disease: the hazard ratio for prostate cancer incidence vs. prostate cancer metastasis and death was 1.69 vs. 1.65 in VIP and 1.25 vs. 1.25 in MDC. PSA was a much stronger predictor of prostate cancer metastasis or death with an area-under-the-curve of 0.78 versus 0.63 for the PRS. Importantly, addition of PRS to PSA did not contribute additional risk stratification for lethal prostate cancer. We have shown that a PRS that predicts prostate cancer incidence does not have utility above and beyond that of PSA measured at baseline when applied to the clinically relevant endpoint of prostate cancer death. These findings have implications for public health policies for delivery of prostate cancer screening. Focusing polygenic risk scores on clinically significant endpoints such as prostate cancer metastasis or death would likely improve clinical utility.

Bone is the most common site for metastasis in human prostate cancer patients. Skeletal metastases are a significant cause of morbidity and mortality and overall greatly affect the quality of life of prostate cancer patients. Despite advances in our understanding of the biology of primary prostate tumors, our knowledge of how and why secondary tumors derived from prostate cancer cells preferentially localize bone remains limited. The physiochemical properties of bone, and signaling molecules including specific chemokines and their receptors, are distinct in nature and function, yet play intricate and significant roles in prostate cancer bone metastasis. Examining the impact of these facets of bone metastasis in vivo remains a significant challenge, as animal models that mimic the natural history and malignant progression clinical prostate cancer are rare. The goals of this article are to discuss (1) characteristics of bone that most likely render it a favorable environment for prostate tumor cell growth, (2) chemokine signaling that is critical in the recruitment and migration of prostate cancer cells to the bone, and (3) current animal models utilized in studying prostate cancer bone metastasis. Further research is necessary to elucidate the mechanisms underlying the extravasation of disseminated prostate cancer cells into the bone and to provide a better understanding of the basis of cancer cell survival within the bone microenvironment. The development of animal models that recapitulate more closely the human clinical scenario of prostate cancer will greatly benefit the generation of better therapies.

The aim of this study was to investigate the possible correlation between prostate volume and aggressiveness and incidence of prostate cancer (PCa).

BACKGROUND The present study aimed to assess the correlation between prostate volume and prostate cancer (PCa) detection by strain elastography (SE)-guided targeted biopsy (TB) compared with conventional transrectal ultrasound (TRUS)-guided systematic biopsy (SB). MATERIAL AND METHODS This retrospective study enrolled 357 patients suspected to have PCa. All patients received TRUS-guided 10-core SB and SE-guided TB. The sensitivity for PCa detected by SE-guided TB was compared with that by TRUS-guided SB, in combination with prostate biopsy pathology. The correlation between the prostate volume and the detection rate of SE-guided TB was investigated. RESULTS PCa was pathologically confirmed in 151 out of 357 patients. The by-patient detection rate of TRUS-guided SB was 72.8% (110/151). Subsequently, a further increase of 6.6% (10/151) in PCa determination was obtained by the SE-guided TB. The sensitivity of SE-guided TB for patients with prostate volume <30 ml, 30-50 ml, 51-80 ml, and >80 ml was 91.7% (44/48), 80.3% (53/66), 70.4% (19/27), and 40.0% (4/10), respectively (p=0.002). For patients with a prostate volume less than 30 ml, SE-guided TB (91.7%) had a higher sensitivity than SB (62.5%) (p<0.007). CONCLUSIONS SE-guided TB has a higher detection rate of PCa in comparison with TRUS-guided SB. There was also a negative correlation between prostate volume and SE-guided TB. Therefore, use of SE-guided TB may complement use of conventional SB, especially for patients with smaller prostate volume.

Prostate cancer (PCa) is the most common malignant neoplasm among men in many countries. Since most precancerous and cancerous tissues show signs of inflammation, chronic bacterial prostatitis has been hypothesized to be a possible etiology. However, establishing a causal relationship between microbial inflammation and PCa requires a comprehensive analysis of the prostate microbiome. The aim of this study was to characterize the microbiome in prostate tissue of PCa patients and investigate its association with tumour clinical characteristics as well as host expression profiles.