Genome-Wide Analysis of Low Dose Bisphenol-A (BPA) Exposure in Human Prostate Cells.

Endocrine disrupting compounds (EDCs) have the potential to cause adverse effects on wild-life and human health. Two important EDCs are the synthetic estrogen 17α-ethynylestradiol (EE2) and bisphenol-A (BPA) both of which are xenoestrogens (XEs) as they bind the estrogen receptor and dis-rupt estrogen physiology in mammals and other vertebrates. In the recent years the influence of XEs on oncogenes, specifically in relation to breast and prostate cancer has been the subject of considerable study. METHODOLOGY: In this study, healthy primary human prostate epithelial cells (PrECs) were exposed to environmentally relevant concentrations of BPA (5nM and 25nM BPA) and interrogated using a whole genome microarray. RESULTS: Exposure to 5 and 25nM BPA resulted in 7,182 and 7,650 differentially expressed (DE) genes, respectively in treated PrECs. Exposure to EE2 had the greatest effect on the PrEC transcriptome (8,891 DE genes). CONCLUSION: We dissected and investigated the nature of the non-estrogenic gene signature associated with BPA with a focus on transcripts relevant to epigenetic modifications. The expression of transcripts encoding nuclear hormone receptors as well as histone and DNA methylation, modifying enzymes were significantly perturbed by exposure to BPA.

Only minor differences in renal osteodystrophy features between wild-type and sclerostin knockout mice with chronic kidney disease.

Renal osteodystrophy affects the majority of patients with advanced chronic kidney disease (CKD) and is characterized by progressive bone loss. This study evaluated the effects of sclerostin knockout on bone in a murine model of severe, surgically induced CKD in both sclerostin knockout and wild-type mice. Mice of both genotypes with normal kidney function served as controls. Tibiae were analyzed using micro-computed tomography, and lumbar vertebrae were analyzed by histomorphometry. Results were tested for statistical significance by 2-way ANOVA to investigate whether bone of the knockout mice reacted differently to CKD compared with bone of wild-type mice. In the tibiae, there was no difference after creation of CKD between wild-type and knockout animals for cortical thickness or cross-sectional moment of inertia. Increases in cortical porosity induced by CKD differed significantly between genotypes in the tibial metaphysis but not in the diaphysis. In the trabecular compartment, no difference in reaction to CKD between genotypes was found for bone volume, trabecular number, trabecular thickness, and trabecular separation. In the lumbar vertebrae, significant differences in response to CKD between wild-type and knockout mice were seen for both bone volume and trabecular thickness. Osteoblast parameters did not differ significantly, whereas osteoclast numbers significantly increased in the wild-type but significantly decreased in knockout mice with CKD. No differences in response to CKD between genotypes were found for bone formation rate or mineral apposition rate. Thus, complete absence of sclerostin has only minor effects on CKD-induced bone loss in mice.

Urine Osmolarity and Risk of Dialysis Initiation in a CKD Cohort.

BACKGROUND: Several experimental studies in rats and a few association studies in humans suggest that the antidiuretic action of vasopressin may accelerate the progression of chronic kidney disease. We undertook a retrospective analysis in a monocentric cohort of 273 patients with chronic kidney disease stages 1-4, focusing on a strong variable of interest, urinary osmolarity, and a strong endpoint, dialysis initiation. Data was analyzed in a multivariate proportional sub-distribution hazards model for competing risk data with appropriate co-variates. MAIN RESULTS: Over a median follow-up period of 92 months, dialysis was initiated in 105 patients. After adjustments for baseline creatinine clearance, and other confounding factors, a higher risk for initiation of dialysis was found in patients with higher urinary osmolarity. After 72 months, the estimated adjusted cumulative incidence probability for dialysis initiation was 15, 24, and 34% in patients with baseline urinary osmolarity of 315, 510, and 775 mosm/l, respectively (p = 0.033). Key Messages: In this retrospective, longitudinal study, a higher baseline urinary osmolarity was strongly associated with a higher risk of end-stage renal disease (after appropriate adjustments). Further, prospective studies are required to evaluate the possible benefit of interventions aiming at reducing urinary osmolarity as a potential treatment for slowing chronic kidney disease progression.

Local shape adaptation for curved slice selection.

PURPOSE: Nonlinear spatial encoding magnetic fields allow excitation and geometrically matched local encoding of curved slices. However, the nonlinearity of the fields results in a varying slice thickness. Within this study, the technique is combined with multidimensional RF excitation for local adaptation of the slice shape. THEORY: A framework originally developed for nonlinear receive encoding is applied to multidimensional excitation with nonlinear spatial encoding magnetic fields for determination of dedicated target patterns and combined with a model for assessment of minimum transmit-resolution requirements for the design of efficient transmit k-space trajectories. METHODS: Cross-sections of curved slices acquired in a phantom with both locally adapted slice thickness and curvature are evaluated. In addition, resulting voxel shapes are analyzed to investigate the range of applicability of the technique. Finally, slice-thickness adaptation is applied to in vivo curved slice imaging. RESULTS: Local adaptation of the slice thickness is feasible both in phantom and in vivo. The technique further allows local adaptation of the slice curvature. However, its range of applicability is limited by prolonged pulse duration and voxel shape distortion. CONCLUSION: Multidimensional excitation allows imaging of curved slices with constant thickness. It also has the potential for further modification of the slice shape for increased ability to adapt to the anatomy.

Direct cerebral and cardiac 17O-MRI at 3 Tesla: initial results at natural abundance.

PURPOSE: To establish direct (17)O-magnetic resonance imaging (MRI) for metabolic imaging at a clinical field strength of 3 T. METHODS: An experimental setup including a surface coil and transmit/receive switch was constructed. Natural abundance in vivo brain images of a volunteer were acquired with a radial three-dimensional (3D) sequence in the visual cortex and in the heart with electrocardiogram (ECG)-gating. RESULTS: In the brain, a signal-to-noise ratio of 36 was found at a nominal resolution of (5.6 mm)(3), and a transverse relaxation time of T(2)* = (1.9 ± 0.2) ms was obtained. In the heart (17)O images were acquired with a temporal resolution of 200 ms. CONCLUSION: Cerebral and cardiac (17)O-MRI at natural abundance is feasible at 3 T.

Sclerostin declines during hemodialysis and appears in Dialysate.

BACKGROUND/AIMS: Sclerostin, a soluble inhibitor of Wnt-signaling, inhibits bone formation. We assessed the impact of dialysis on serum sclerostin and whether sclerostin is detectable in effluent dialysates. METHODS: In a prospective study of 54 prevalent hemodialysis patients, parameters of bone and mineral metabolism were assessed at the beginning and at the end of dialysis. In a subset of patients (n = 19) sclerostin was measured in serum at start, 1, 2, and 3 h of dialysis and in the effluent dialysate at several points in time. RESULTS: Sclerostin serum levels decreased from median 71.4 pmol/l to 43.5 pmol/l during dialysis (p < 0.0001). In patients with high pre-dialysis sclerostin serum levels, sclerostin was detected in the dialysate. Higher Kt/V correlated with greater relative decrease of sclerostin (r = 0.467; p = 0.001). CONCLUSION: Sclerostin is dialysable. Furthermore, sclerostin serum levels decrease during dialysis. Whether targeting lower sclerostin levels by means of improved dialysis adequacy has direct relevance to bone disease remains to be shown.

Inner-volume imaging in vivo using three-dimensional parallel spatially selective excitation.

This work describes the first experimental realization of three-dimensional spatially selective excitation using parallel transmission in vivo. For the design of three-dimensional parallel excitation pulses with short durations and high excitation accuracy, the choice of a suitable transmit k-space trajectory is crucial. For this reason, the characteristics of a stack-of-spirals trajectory and of a concentric-shells trajectory were examined in an initial simulation study. It showed that, especially when undersampling the trajectories in combination with parallel transmission, experimental parameters such as transmit-coil geometry and off-resonance conditions have an essential impact on the suitability of the selected trajectory and undersampling scheme. Both trajectories were applied in MR inner-volume imaging experiments which demonstrate that acceptably short and robust three-dimensional selective pulses can be achieved if the trajectory is temporally optimized and its actual path is measured and considered during pulse calculation. Pulse durations as short as 3.2 ms were realized and such pulses were appropriate to accurately excite arbitrarily shaped volumes in a corn cob and in a rat in vivo. Reduced field-of-view imaging of these selectively excited targets allowed high spatial resolution and significantly reduced measurement times and furthermore demonstrates the feasibility of three-dimensional parallel excitation in realistic MRI applications in vivo.

The CD95/CD95L pathway is involved in phagocytosis-induced cell death of monocytes and may account for sustained inflammation in neonates.

BACKGROUND: The propensity for sustained inflammation after bacterial infection in neonates, resulting in inflammatory sequelae such as bronchopulmonary dysplasia and periventricular leucomalacia, is well known, but its molecular mechanisms remain elusive. Termination of inflammatory reactions physiologically occurs early after removal of bacteria by phagocytosis-induced cell death (PICD) of immune effector cells such as monocytes. PICD from cord blood monocytes (CBMOs) was shown to be reduced as compared with that of peripheral blood monocytes (PBMOs) from adult donors in vitro. METHODS: PBMOs, CBMOs, and Fas (CD95)-deficient (lpr) mouse monocytes were analyzed in an in vitro infection model using green fluorescence protein-labeled Escherichia coli (E. coli-GFP). Phagocytosis and apoptosis were quantified by flow cytometry and CD95L secretion was quantified by enzyme-linked immunosorbent assay. RESULTS: We demonstrate the involvement of the CD95/CD95 ligand pathway (CD95/CD95L) in PICD and provide evidence that diminished CD95L secretion by CBMOs may result in prolonged activation of neonatal immune effector cells. CONCLUSION: These in vitro results offer for the first time a molecular mechanism accounting for sustained inflammation seen in neonates.

Iterative separation of transmit and receive phase contributions and B1(+)-based estimation of the specific absorption rate for transmit arrays.

OBJECT: The specific absorption rate (SAR) can be determined from radiofrequency transmit fields measured via magnetic resonance imaging. MATERIALS AND METHODS: The proposed method estimates the SAR solely from the complex transmit field (B1(+)) by taking into account the particular properties of the electromagnetic field generated by an 8-channel transmit array. It is further based on an iterative consistency check between the measured B1(+) magnitude and an appropriate field estimate fulfilling Maxwell's equations. For testing the method, simulations and phantom experiments were performed for a multi-transmit array at 3T using a cylindrical phantom. RESULTS: The method's robustness with respect to the assumptions made about electric tissue properties as well as its stability under different initial conditions regarding the signal phase was shown. A high sensitivity to signal noise was found. Robust reconstruction results were achieved including information from more than two transmit elements. The validity of the experimental results was confirmed by a qualitative comparison to simulated electromagnetic fields. CONCLUSIONS: The method allows the determination of the SAR as well as the transmit phase of the individual channels of a multi-transmit array. With additional B0 inhomogeneity measurements, a reconstruction of the receive phase is feasible independent of the receive coil type in use.

Selective excitation of two-dimensional arbitrarily shaped voxels with parallel excitation in spectroscopy.

Parallel excitation is being studied intensively for applications in MR imaging and in particular for selecting arbitrary shapes as regions of interest. In this work, parallel excitation was applied to arbitrarily shaped voxel selection in spectroscopy and investigated for different excitation k-space trajectories (radial, rectilinear, and spiral) and acceleration factors. Each trajectory was segmented into multiple excitations to increase the overall bandwidth during target selection. Acceleration by parallel excitation was used to decrease the number of segments. Evaluation of spatial and spectral localization of the target of interest was performed in simulation and phantom experiments, and was compared with the point resolved spectroscopy (PRESS) experiment with standard voxels. The selective excitation experiments demonstrated excellent spatial localization and a broad frequency response, although PRESS was superior in direct comparisons with respect to signal-to-noise ratio (SNR) and outer volume suppression. Extensive SNR variation was observed dependent on trajectory (8%-90%), with the preferred radial case producing approximately 40%-60% SNR of the PRESS case. Accelerated trajectories at R = 4 provided comparable artifact signal and target excitation accuracy compared with their nonaccelerated counterparts; however, further acceleration (R = 8) resulted in increased artifact (33% increase at R = 8).

Three-dimensional arbitrary voxel shapes in spectroscopy with submillisecond TEs.

A novel spectroscopic method for submillisecond TEs and three-dimensional arbitrarily shaped voxels was developed and applied to phantom and in vivo measurements, with additional parallel excitation (PEX) implementation. A segmented spherical shell excitation trajectory was used in combination with appropriate radiofrequency weights for target selection in three dimensions. Measurements in a two-compartment phantom realized a TE of 955 µs, excellent spectral quality and comparable signal-to-noise ratios between accelerated (R = 2) and nonaccelerated modes. The two-compartment model allowed a comparison of the spectral suppression qualities of the method and, although outer volume signals were suppressed by factors of 1434 and 2246 compared with the theoretical unsuppressed case for the clinical and PEX modes, respectively, incomplete suppression of the outer volume (935 cm(3) compared with a target volume of 5.86 cm(3) ) resulted in a spectral contamination of 10.2% and 6.5% compared with the total signal. The method was also demonstrated in vivo in human brain on a clinical system at TE = 935 µs with good signal-to-noise ratio and spatial and spectral selection, and included LCModel relative quantification analysis. Eight metabolites showed significant fitting accuracy, including aspartate, N-acetylaspartylglutamate, glutathione and glutamate.

Sclerostin serum levels correlate positively with bone mineral density and microarchitecture in haemodialysis patients.

BACKGROUND: Sclerostin is a soluble inhibitor of osteoblast function. Sclerostin is downregulated by the parathyroid hormone (PTH). Here, it was investigated whether sclerostin levels are influenced by intact (i) PTH and whether sclerostin is associated with bone turnover, microarchitecture and mass in dialysis patients. METHODS: Seventy-six haemodialysis patients and 45 healthy controls were included in this cross-sectional study. Sclerostin, Dickkopf-1 (DKK-1), intact parathyroid hormone (iPTH), vitamin D and markers of bone turnover were analysed. A subset of 37 dialysis patients had measurements of bone mineral density (BMD) using dual-energy X-ray absorptiometry and bone microarchitecture using high-resolution peripheral quantitative computed tomography. RESULTS: Dialysis patients had significantly higher sclerostin levels than controls (1257 pg/mL versus 415 pg/mL, P < 0.001). Significant correlations were found between sclerostin and gender (R = 0.41), iPTH (R = -0.28), 25-hydroxy-cholecalciferol (R = 0.27) and calcium (R = 0.25). Gender and iPTH remained significantly associated with sclerostin in a multivariate analysis. Sclerostin serum levels were positively associated with BMD at the lumbar spine (R = 0.46), femoral neck (R = 0.36) and distal radius (R = 0.42) and correlated positively mainly with trabecular structures such as trabecular density and number at the radius and tibia in dialysis patients. DKK-1 was related neither to bone measures nor to serologic parameters. CONCLUSIONS: Considering that sclerostin is an inhibitor of bone formation, the observed positive correlations of serum sclerostin with BMD and bone volume were unexpected. Whether its increase in dialysis patients has direct pathogenetic relevance or is only a secondary phenomenon remains to be seen.

Robust spatially selective excitation using radiofrequency pulses adapted to the effective spatially encoding magnetic fields.

Multidimensional spatially selective excitation (SSE) has stimulated a variety of useful applications in magnetic resonance imaging and magnetic resonance spectroscopy, which have regained considerable interest after the recent introduction of parallel excitation. For SSE, radiofrequency pulses are designed specifically for certain time-courses of spatially encoding magnetic fields (SEM) which are applied simultaneously with the radiofrequency pulses. However, experimental imperfections of gradient-systems and undesired SEM field contributions often prevent the correct co-action of radiofrequency pulses and gradient-waveforms and therefore degrade the fidelity of excitation patterns, especially for parallel excitation. To cope with such imperfections, a classical measurement of k-space-trajectories can be performed followed by an adaptation of the SSE-pulses. However, this method is limited to linear SEM field distributions, which are describable in the k-space-formalism. Hence, this work presents a more sophisticated method consisting in a spatially resolved measurement of the temporal phase evolution of the transverse magnetization. This exhaustive phase information can be incorporated into pulse-design algorithms to compensate even for undesired spatially nonlinear, dynamic SEM field contributions. Both approaches are assessed in various experimental scenarios and individual benefits and limitations are discussed. The adaptation of SSE-pulses to experimentally achieved calibration data turned out to be very beneficial, and especially the novel spatially resolved method exhibited high potential for robust SSE even in adverse experimental setups.

The effect of fluid intake on chronic kidney transplant failure: a pilot study.

OBJECTIVE: Transplant recipients are generally instructed to increase their daily fluid intake so as to preserve kidney function. However, studies supporting this hypothesis are lacking. SETTING: Prospective, randomized study at a tertiary care university hospital. PATIENTS: Patients with chronic kidney transplant failure. INTERVENTION: Assignment to normal fluid intake (NFI: 2 L/day) or high fluid intake (HFI: 4 L/day) for 12 months. MAIN OUTCOME MEASURE: The effect of fluid intake on the decrease in estimated glomerular filtration rate (eGFR) was estimated by a mixed-effects general linear model. The analysis was adjusted for the observation period, age, intake of angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers, diuretics, and transplant duration. RESULTS: A total of 33 patients were randomized to NFI and 29 to HFI. After 12 months, the mean eGFR had decreased to a similar extent in both groups (NFI: 44 ± 9 mL/min vs. 41 ± 9 mL/min; HFI: 46 ± 15 mL/min vs. 44 ± 15 mL/min). In the multivariate analysis, only the observation period had a significant effect on the decrease in eGFR. Randomization to NFI or HFI nor any other variable was associated with kidney function. The association between urine volume and urine osmolality was lost after 12 months. CONCLUSIONS: Recommendation of higher fluid intake does not seem to improve chronic kidney transplant failure. However, the lack of association between urine osmolality and reported urine volume at a later stage implies a loss of adherence to fluid intake over time.

Characterization of FGFR signaling in prostate cancer stem cells and inhibition via TKI treatment.

Metastatic castrate-resistant prostate cancer (CRPC) remains uncurable and novel therapies are needed to better treat patients. Aberrant Fibroblast Growth Factor Receptor (FGFR) signaling has been implicated in advanced prostate cancer (PCa), and FGFR1 is suggested to be a promising therapeutic target along with current androgen deprivation therapy. We established a novel in vitro 3D culture system to study endogenous FGFR signaling in a rare subpopulation of prostate cancer stem cells (CSCs) in the cell lines PC3, DU145, LNCaP, and the induced pluripotent iPS87 cell line. 3D-propagation of PCa cells generated spheroids with increased stemness markers ALDH7A1 and OCT4, while inhibition of FGFR signaling by BGJ398 or Dovitinib decreased cell survival and proliferation of 3D spheroids. The 3D spheroids exhibited altered expression of EMT markers associated with metastasis such as E-cadherin, vimentin and Snail, compared to 2D monolayer cells. TKI treatment did not result in significant changes of EMT markers, however, specific inhibition of FGFR signaling by BGJ398 showed more favorable molecular-level changes than treatment with the multi-RTK inhibitor Dovitinib. This study provides evidence for the first time that FGFR1 plays an essential role in the proliferation of PCa CSCs at a molecular and cellular level, and suggests that TKI targeting of FGFR signaling may be a promising strategy for AR-independent CRPC.

The risk of death in patients with a high coronary calcification score: does it include predialysis patients?

High coronary artery calcification score (CACS) assessed by computed tomography is related to mortality in asymptomatic patients with normal kidney function. The predictive value of CACS is still disputed in patients with end-stage renal disease and is unknown in patients with pre-terminal renal failure. Chiu and co-workers provide evidence that CACS is associated with mortality also in patients with chronic kidney disease not yet on dialysis.

Cinacalcet decreases bone formation rate in hypercalcemic hyperparathyroidism after kidney transplantation.

BACKGROUND/AIMS: Cinacalcet reduces serum calcium in kidney transplant recipients with hypercalcemic hyperparathyroidism. Its effect on bone, however, has not been investigated in this population. METHODS: We prospectively examined bone turnover, histomorphometry and density as well as serum bone biomarkers in 10 transplant recipients before and after treatment with cinacalcet. RESULTS: After 18-24 months of treatment with cinacalcet, bone formation decreased in 7, increased in 2, and remained zero in 1 patient (p = 0.11). Trabecular bone volume was maintained. Trabecular number decreased (p = 0.03), but trabecular thickness was unchanged (p = 0.17). Osteoid decreased (p = 0.02) and osteoblast surface increased (p = 0.02). Bone mineral density of the femur remained stable in 1 patient, decreased in 2 patients, but increased in 7 patients (p = 0.153). Serum calcium concentration (p = 0.005), iPTH (p = 0.01) and calcitonin concentration decreased (p = 0.03), while 25(OH) vitamin D(3) increased (p = 0.02). No fractures were reported. Graft function remained stable. CONCLUSION: While cinacalcet might decrease bone formation rate, it did not change bone volume, and bone mineral density of the femur increased. Therefore, the use of cinacalcet in hypercalcemic hyperparathyroidism might be safe with regard to the bone disease present after kidney transplantation.

Treatment of Hemodialysis-Associated Adynamic Bone Disease with Teriparatide (PTH1-34): A Pilot Study.

BACKGROUND: Adynamic bone disease (ABD) is caused by a relative or absolute parathyroid hormone (PTH) deficiency. Teriparatide (PTH1-34) is an osteoanabolic agent in clinical use. Here, it was hypothesized that treatment with teriparatide improves bone mineral density (BMD) of ABD patients. PATIENTS AND METHODS: Seven hemodialysis patients with ABD and a median iPTH level of 22 pg/ml were evaluated in this open-label, prospective, 6-month observational pilot-study. All patients received 20 µg teriparatide/day subcutaneously. Serologic bone markers, BMD and coronary artery calcification (CAC) were measured at baseline and after 6 months. RESULTS: Teriparatide therapy led to a significant increase in lumbar spine (0.885 ± 0.08 vs. 0.914 ± 0.09 g/cm(2), p < 0.02), but not femoral neck (0.666 ± 0.170 vs. 0.710 ± 0.189 g/cm(2), p = 0.18) BMD. Compared to pretreatment values, calculated monthly changes in BMD improved significantly in both the lumbar spine and femoral neck (p < 0.02). Changes in serologic markers of bone turnover and CAC scores were not statistically significant. CONCLUSION: Teriparatide therapy might improve low BMD in hemodialysis patients with ABD. Further clinical studies are needed to establish teriparatide as a therapeutic option for dialysis patients with ABD.

Characterization of iPS87, a prostate cancer stem cell-like cell line.

Prostate cancer affects hundreds of thousands of men and families throughout the world. Although chemotherapy, radiation, surgery, and androgen deprivation therapy are applied, these therapies do not cure metastatic prostate cancer. Patients treated by androgen deprivation often develop castration resistant prostate cancer which is incurable. Novel approaches of treatment are clearly necessary. We have previously shown that prostate cancer originates as a stem cell disease. A prostate cancer patient sample, #87, obtained from prostatectomy surgery, was collected and frozen as single cell suspension. Cancer stem cell cultures were grown, single cell-cloned, and shown to be tumorigenic in SCID mice. However, outside its natural niche, the cultured prostate cancer stem cells lost their tumor-inducing capability and stem cell marker expression after approximately 8 transfers at a 1:3 split ratio. Tumor-inducing activity could be restored by inducing the cells to pluripotency using the method of Yamanaka. Cultures of human prostate-derived normal epithelial cells acquired from commercial sources were similarly induced to pluripotency and these did not acquire a tumor phenotype in vivo. To characterize the iPS87 cell line, cells were stained with antibodies to various markers of stem cells including: ALDH7A1, LGR5, Oct4, Nanog, Sox2, Androgen Receptor, and Retinoid X Receptor. These markers were found to be expressed by iPS87 cells, and the high tumorigenicity in SCID mice of iPS87 was confirmed by histopathology. This research thus characterizes the iPS87 cell line as a cancer-inducing, stem cell-like cell line, which can be used in the development of novel treatments for prostate cancer.

Influence of Intratumor Microbiome on Clinical Outcome and Immune Processes in Prostate Cancer.

Although 1 in 9 American men will receive a diagnosis of prostate cancer (PC), most men with this diagnosis will not die from it, as most PCs are indolent. However, there is a subset of patients in which the once-indolent PC becomes metastatic and eventually, fatal. In this study, we analyzed microbial compositions of intratumor bacteria in PC to determine the influence of the microbiome on metastatic growth. Using large-scale RNA-sequencing data and corresponding clinical data, we correlated the abundance of microbes to immune pathways and PC risk factors, identifying specific microbes that either significantly deter or contribute to cancer aggressiveness. Interestingly, most of the microbes we found appeared to play anti-tumor roles in PC. Since these anti-tumor microbes were overrepresented in tumor samples, we believe that microbes thrive in the tumor microenvironment, outcompete cancer cells, and directly mitigate tumor growth by recruiting immune cells. These include Listeria monocytogenes, Methylobacterium radiotolerans JCM 2831, Xanthomonas albilineans GPE PC73, and Bradyrhizobium japonicum, which are negatively correlated with Gleason score, Tumor-Node-Metastasis (TNM) stage, prostate-specific antigen (PSA) level, and Androgen Receptor (AR) expression, respectively. We also identified microbes that contribute to tumor growth and are positively correlated with genomic alterations, dysregulated immune-associated (IA) genes, and prostate cancer stem cells (PCSC) genes.