Single-cell RNA-seq analysis of benign prostatic hyperplasia prostate specimens stratified by prostate weight
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE330752 | GEO | 2026/07/20
REPOSITORIES: GEO
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Project description:There is an unmet need for improved diagnostic testing and risk prediction for cases of prostate cancer (PCa) to improve care and reduce overtreatment of indolent disease. Here we have analysed the serum proteome and lipidome of 262 study participants by liquid chromatography-mass spectrometry, including participants with a diagnosis of PCa, benign prostatic hyperplasia (BPH), or otherwise healthy volunteers, with the aim of improving biomarker specificity. Although a two-class machine learning model was able to separate PCa from controls with sensitivity of 0.82 and specificity of 0.95, adding BPH resulted in a statistically significant decline in specificity for prostate cancer to 0.76, with half of BPH cases being misclassified by the model as PCa. A small number of biomarkers differentiating between BPH and prostate cancer were identified, including proteins in MAP Kinase pathways, as well as in lipids containing oleic acid; these may offer a route to greater specificity. These results highlight, however, that whilst there are opportunities for machine learning, these will only be achieved by use of appropriate training sets that include confounding comorbidities, especially when calculating the specificity of a test.
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Project description:BPH samples harbored minimal copy number alterations, and the fraction of altered genome was far lower than primary prostate cancer and other neoplastic diseases.
2020-03-18 | GSE124187 | GEO
Project description:Benign prostatic hyperplasia (BPH) is characterized by excessive cell proliferation and inflammation and affects most aging men. The development of new therapies for BPH requires a deeper understanding of the underlying pathophysiology and cellular components of BPH. Single-cell RNA-sequencing was performed on prostate tissue from 15 patients undergoing holmium laser enucleation of the prostate for treatment of BPH. Clustering and differential expression analysis on aligned single cell RNA-seq data was performed to annotate all cell types. 16,234 cells were analyzed and specific stromal, epithelial, and immune subgroups were found to be strongly associated with inflammation. A rare luminal subgroup was identified and pseudotime analysis indicated this luminal subgroup might give rise to other luminal cells. Using a gene set derived from epithelial stem cells, we found that this luminal subgroup had a significantly higher stem cell signature score than all other epithelial subgroups, suggesting this subgroup is a luminal precursor state. Ligand-receptor interactions between stromal, epithelial, and immune cells were explored with CellPhoneDB. Significant interactions involving MIF, a pro-inflammatory cytokine that promotes epithelial cell growth and inflammatory response in the prostate, were identified between the progenitor-like luminal subgroup and both fibroblasts and macrophages. Our single-cell profiling of BPH provides a roadmap for investigating inflammation-linked cell subgroups and highlights a progenitor-like luminal subgroup interacting with other cell groups via MIF that may contribute to the inflammation and cell proliferation phenotype associated with BPH.
2026-02-25 | GSE290213 | GEO
Project description:Steroid 5 alpha-reductase type 2 (SRD5A2) is a key enzyme in androgen metabolism and a pharmacologic target in benign prostatic hyperplasia (BPH). While SRD5A2 is known to mediate stromal-epithelial interactions that influence prostate growth, the relationship between baseline SRD5A2 expression and prostate volume remains unclear. In this study, we analyzed SRD5A2 expression in human prostate tissues from the Medical Therapy of Prostatic Symptoms (MTOPS) trial and institutional biorepository cohorts. Quantitative assessments were performed and correlations were evaluated between expression level of SRD5A2, WNT5A, prostate volume, and tissue signaling profiles. SRD5A2 expression was significantly associated with total prostate and transition zone volume. Stromal-specific WNT5A expression showed a strong positive correlation with SRD5A2, while neither serum nor tissue dihydrotestosterone levels correlated with SRD5A2 expression. In Srd5a2-null mice, Wnt5a expression in the prostate stroma was dependent on Srd5a2 and showed region-specific regulation. Mechanistically, SRD5A2 overexpression in human prostate stromal cells upregulated WNT5A and Lymphoid Enhancer-Binding Factor 1 (LEF1), activated insulin-like growth factor 1 (IGF1) signaling, increased proliferation, and reduced apoptosis. Conditioned media from these cells enhanced epithelial proliferation through paracrine IGF1 activity. This study provides the first evidence that SRD5A2 promotes prostate growth through a stromal WNT5A-LEF1-IGF1 paracrine signaling axis independent of androgen levels, suggesting a novel therapeutic mechanism relevant for BPH patients with resistance to conventional 5 alpha-reductase inhibitor therapy.
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Project description:Prostate cancer (PCa) remains a prevalent and deadly disease. The histology-based Gleason score (GS) of PCa tissue biopsy is the most accurate predictor of disease aggressiveness and an important measure to guide decision-making with respect to treatment strategies and patient management. However, inherent variability associated with PCa tumour sampling and the subjective determination of the GS are still key challenges precluding accurate diagnostication and prognostication. Thus, novel molecular signatures are urgently needed to distinguish between indolent and aggressive forms of PCa for better patient management and outcomes. Herein, we have used label-free LC-MS/MS-based proteomics to profile the proteome of 50 PCa tissues spanning five GS-based PCa grades (n = 10 per group) relative to five tissues from individuals with benign prostatic hyperplasia (BPH). Over 2,000 proteins were consistently identified albeit at different levels between and within the patient groups, revealing biological processes associated with specific grades. Excitingly, a panel of 11 prostate-derived proteins including IGKV3D-20, RNASET2, TACC2, ANXA7, LMOD1, PRCP, GYG1, NDUFV1, H1FX, APOBEC3C, CTSZ displayed the potential to accurately stratify patients displaying low and high GS. This is the first study to characterise the prostate tissue proteome signatures of the five PCa grades relative to BPH. We report a panel of proteins that accurately can distinguish low and high GS PCa tissues. These promising proteins can be further explored as candidate biomarkers for PCa aggressiveness.
2019-10-09 | PXD013837 | Pride
Project description:Benign prostatic hyperplasia (BPH) is difficult to discriminate from prostate carcinoma (PCa) preoperatively. The non-invasive biomarkers are necessary to reduce the burden of biopsies and improve survival quality of patients. Previous research suggests that abnormal glycosylation of immunoglobulin gamma molecules (IgGs) may associated with immunological diseases and prostate diseases. Hence, characterizing intact N-glycopeptides of IgGs that correspond to N-glycan structure with specific site information enable better understanding of the molecular pathogenesis and finding out some novel signatures in preoperative discrimination of BPH from PCa. In this study, we profiled intact N-glycopeptides of purified IgGs from 51 PCa patients and 45 BPH patients by our developed N-glycoproteomic method using hydrophilic interaction liquid chromatography enrichment coupled with high resolution LC-MS/MS, and intact N-glycopeptides quantitative analysis was performed using pGlyco 2.0 and MaxQuant softwares. Our data provided plasma IgG subclass-specific and site-specific N-glycosylation quantitative information.
2020-06-29 | PXD016175 | Pride
Project description:Macrophages exhibit marked phenotypic heterogeneity within and across disease states. Lipid metabolic reprogramming critically regulates macrophage activation. Chronic inflammation has been observed in human benign prostatic hyperplasia (BPH) tissues, however macrophage activation states and their contributions to this hyperplastic disease have not been defined. We postulated that a shift in macrophage phenotypes with increasing prostate size could involve metabolic alterations resulting in prostatic epithelial or stromal hyperplasia. Single-cell RNA-seq of CD45+ transition zone leukocytes from 10 large (>90 grams) and 10 small (<40 grams) human prostates was conducted. Macrophage subpopulations were defined using marker genes. BPH macrophages do not distinctly categorize into M1 and M2 phenotypes. Instead, macrophages with neither polarization signature accumulate in large versus small prostates. Specifically, macrophage subpopulations with altered lipid metabolism pathways, demarcated by TREM2 and MARCO expression, significantly accumulate as prostate size increases. No T cell subclusters specifically accumulate in large versus small prostates. TREM2+ and MARCO+ macrophage abundance positively correlates with patient body mass index and prostatic symptom scores. TREM2+ macrophages have significantly higher neutral lipid than TREM2- macrophages from BPH tissues. Lipid-rich macrophages localize to the stroma in BPH tissues. In vitro studies indicate that lipid-loaded macrophages increase prostate epithelial and stromal cell proliferation compared to control macrophages. These data define new BPH immune subpopulations, TREM2+ and MARCO+ macrophages, and suggest that lipid-rich macrophages may exacerbate lower urinary tract symptoms in patients with large prostates. Further investigation is needed to evaluate the therapeutic benefit of targeting these cells in BPH.
2025-01-13 | GSE269205 | GEO
Project description:To identify the genes differently expressed in the epithelium and the stromal of Benign Prostatic Hyperplasia (BPH), we collect the epithelium and the stromal from the patients with benign prostatic hyperplasia by laser micro-dissection. And then, Affymetrix HG-U133_Plus_2 gene-chip was used to detect and compare the expression level of genes. To find which genes are most abundantly expressed in epithelium and stromal and what is the role of these genes in the pathogenesis of BPH. 8 prostate tissues were collected from patients undergone transurethral resection of the prostate (TURP) with informed consent. Each tissue was embedded in O.C.T and subsequently used for laser micro-dissection. The total RNA was isolated from each sample and equally mixed for gene-chip assay.
2011-08-09 | E-GEOD-31323 | biostudies-arrayexpress
Project description:It is well known that prostate cancer (PCa) is a progressive disease involving multiple gene alterations. The Gleason score (GS) is a morphologic feature of PCa used in the clinic to evaluate the risk of disease progression. However, GS often fail to clearly distinguish between indolent and aggressive disease. The aim of this study was to identify potential biomarkers for PCa risk stratification. An in-depth proteomics analysis (LC ESI-MS/MS) was performed on human PCa and BPH tissues. First, we identified differentially expressed proteins between PCa and BPH samples. We then filtered the proteins based on peptide spectrum matches and selected a panel of candidates. To assess and validate the clinical significance of these peptides we performed an integrative bioinformatics analysis using public database repositories. We identified YWHAZ, an androgen receptor downstream target, as one of the proteins enriched in PCa compared with BPH. We also found a strong association of YWHAZ expression with poor prognosis across different PCa datasets. Briefly, overall and relapse-free survival were significantly shorter in PCa cases expressing high vs. low YWHAZ expression. Further, multivariate analyses displayed high significant correlation with poor prognosis, independent from GS, age, PSA at diagnosis and TMPRSS2-ERG fusion. A multi-cancer screening for YWHAZ unveils amplification as the main alteration for this gene correlating with increased mRNA expression levels across all types of cancer through the cBioPortal platform. YWHAZ rises as a promising prognostic factor in PCa, independent from GS, aiding in disease risk stratification.
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Project description:Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms affect a large percentage of the male population and places a substantial burden on the world health system. Current therapies include 5-alpha reductase inhibitors and alpha-blockers that are only partially effective and pose a huge economic burden, emphasizing the urgent need for effective, economical therapies. We isolated nanovesicles from pomegranate juice (Punica Granatum) (referred to as ‘POM-NVs’) and report to our knowledge for the first time, that these vesicles possess therapeutic potential against BPH. Following extensive characterization of POM-NVs, we tested their therapeutic potential in vitro using BPH1 cell line and identified a potential anti-proliferative and pro-apoptotic effect. We further tested these vesicles using a clinically relevant xenograft mouse BPH model derived from human BPH tissues. Remarkably, POM-NVs could reverse the BPH phenotype conferred by TGF-β mediated signaling and induced epithelial-to-mesenchymal (EMT) reversal, leading to the restoration of prostate epithelial states in vivo and in vitro. Furthermore, these vesicles attenuated bone morphogenic protein 5 (BMP5) signaling, a cardinal alteration that is instrumental in driving BPH. Considering the large incidences of BPH and its associated economic burdens, our study has important implications and can potentially improve the clinical management of BPH.
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