Differential gene expression analysis by assessing transcriptome-wide expression variation between tissue specimen of prostate cancer (PCa) and benign prostate hyperplasia (BPH)
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA553688 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We assessed differential gene expression in tissue specimens of PCa and BPH patients who underwent radical prostatectomy by next-generation sequencing (HiSeq 2000). We stratified PCa patients according to seven clinical risk groups based on Gleason Score (GS), the presence of regional lymph node metastases (pN) and the occurrence of death of disease (DoD): (i) very low risk (group V: GS<7, pN0), (ii) low risk (group L: GS=7, pN0), (iii) medium risk (group M: GS<=7, pN1), (iv) high risk survivors without lymph node infiltration (group H-s: GS>7, pN0), (v) high risk non-survivors without lymph node infiltration (group H-d: GS>7, pN0, DoD), (vi) high risk survivors with lymph node infiltration (group H+s: GS>7, pN1), (vii) high risk non-survivors with lymph node infiltration (group H+d: GS>7, pN1, DoD). For high risk groups adjacent tumor-free prostate tissue samples were obtained (groups H+sf, H-sf, H+df, H+df). The control group contained patients with benign prostate hyperplasia (group C). Information on the course of the disease, survival of the patients and the cause of death were obtained from the general practitioners or treating urologists or from records of the regional tumor registry. Clinicopathological parameters were obtained by routine histopathological examination of the surgical specimens. Serum levels of the prostate-specific antigen (PSA) were determined preoperatively (Abbott, Wiesbaden, Germany). Frozen tissue samples were embedded in Tissue-Tek OCT-compound (Sakura Finetek GmbH, Staufen im Breisgau, Germany) and fixed on metal indenters by freezing. Cryo-sections were prepared using a cryo-microtome (Leica Biosystems, Nußloch, Germany) equipped with a microtome blade C35 cooled to -28 °C. For every tissue three stacks of consecutive cryo-sections (10 µm) were generated, each bordered/flanked by HE-stained cryo-sections (4 µm), which were evaluated by a pathologist with regard to tumor and stroma cell content. PCa tissue stacks had to be flanked on either side by sections containing at least 50 % tumor cells to be used for further analyses. Sections of the tissue stacks were immediately transferred to 1 ml Qiazol (Qiagen, Hilden, Germany) and stored at -80 °C until RNA isolation.
2020-06-17 | GSE134073 | GEO
Project description:We assessed differential gene expression in tissue specimens of PCa and BPH patients who underwent radical prostatectomy by customized expression microarrays (Agilent). To detect gene signatures of diagnostic and prognostic value, we assessed fresh frozen radical prostatectomy (RP) samples of PCa and BPH patients by transcriptome-wide sequencing and Agilent custom microarrays. We stratified PCa patients according to seven clinical risk groups based on Gleason Score (GS), the presence of regional lymph node metastases (pN) and the occurrence of death of disease (DoD): (i) very low risk (group V: GS<7, pN0), (ii) low risk (group L: GS=7, pN0), (iii) medium risk (group M: GS<=7, pN1), (iv) high risk survivors without lymph node infiltration (group H-s: GS>7, pN0), (v) high risk non-survivors without lymph node infiltration (group H-d: GS>7, pN0, DoD), (vi) high risk survivors with lymph node infiltration (group H+s: GS>7, pN1), (vii) high risk non-survivors with lymph node infiltration (group H+d: GS>7, pN1, DoD). For high risk groups adjacent tumor-free prostate tissue samples were obtained (groups H+sf, H-sf, H+df, H+df). The control group contained patients with benign prostate hyperplasia (group C). Information on the course of the disease, survival of the patients and the cause of death were obtained from the general practitioners or treating urologists or from records of the regional tumor registry. Clinicopathological parameters were obtained by routine histopathological examination of the surgical specimens. Serum levels of the prostate-specific antigen (PSA) were determined preoperatively (Abbott, Wiesbaden, Germany). Frozen tissue samples were embedded in Tissue-Tek OCT-compound (Sakura Finetek GmbH, Staufen im Breisgau, Germany) and fixed on metal indenters by freezing. Cryo-sections were prepared using a cryo-microtome (Leica Biosystems, Nußloch, Germany) equipped with a microtome blade C35 cooled to -28 °C. For every tissue three stacks of consecutive cryo-sections (10 µm) were generated, each bordered/flanked by HE-stained cryo-sections (4 µm), which were evaluated by a pathologist with regard to tumor and stroma cell content. PCa tissue stacks had to be flanked on either side by sections containing at least 50 % tumor cells to be used for further analyses. Sections of the tissue stacks were immediately transferred to 1 ml Qiazol (Qiagen, Hilden, Germany) and stored at -80 °C until RNA isolation.
2020-06-17 | GSE134051 | GEO
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.
2024-01-26 | PXD046530 | Pride
Project description:Copy number variations (CNVs) in the human genome have been linked to various carcinomas including prostate cancer (PCa). This study was conducted to identify CNVs in high grade PCa. We performed a pilot genome-wide CNV analysis in 36 subjects (18 high grade PCa and 18 benign prostatic hyperplasia) using array comparative genomic hybridization (aCGH) technique. Array results were validated using PCR-based copy number counting method. A total of 339 CNV regions were found to be unique to PCa subjects in this cohort (P < 0.05). Data segregation and filtering revealed six putative CNV loci associated with susceptibility to PCa. Of these, four were rare (1q21.3, 15q15, 3q27.2 and 7p12.1) and one was a novel copy number gain (12q23.1), harbouring genes such as the ARNT, THBS1, SLC5A8 and DDC which are crucial in the p53 and cancer pathways. Another CNV was a loss at 8p11.21 which contains the SFRP1 gene from the Wnt signalling pathway, known for its interaction with androgen receptors as reported for urological malignancy. Cross comparison analysis with genes already known to be associated with PCa revealed significant CNVs involved in crucial biological processes that elicit cancer pathogenesis via cytokine production, disease progression through endothelial cell proliferation and xenobiotic metabolism. In conclusion, these findings suggest that the CNV regions identified could provide an insight into the development of high grade PCa.
2018-12-18 | GSE79402 | GEO
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: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.
2021-09-08 | PXD014291 | Pride
Project description:Differential gene expression analysis by assessing expression variation between tissue specimen of prostate cancer (PCa) and benign prostate hyperplasia (BPH) on a custom expression microarray
| PRJNA553569 | ENA
Project description:African American (AA) men have higher prostate cancer (PCa) incidence and mortality rates than any other racial/ethnic group in the USA. Biological differences including aberrant epigenetic DNA methylation changes likely contribute to the PCa disparities. Our study aims to identify differentially methylated CpG sites and genes among histologic localized adenocarcinoma PCa, metastatic PCa (mCRPC), and Benign Prostatic Hyperplasia (BPH) samples. We performed genome-wide DNA methylation profiling in 100 AA prostate tissues using Illumina Methylation EPIC array. Global hypermethylation indicating epigenetic silence was observed in localized adenocarcinoma PCa compared to paired normal and BPH samples. On the other hand, significant hypomethylation suggesting tumor associated activation of oncogenes and chromatin remodeling was observed in mCRPC. Using Shannon entropy as a metric for epigenetic heterogeneity, mCRPC samples exhibited significant elevated entropy, reflecting greater methylation variability than localized adenocarcinoma PCa and BPH. We also identified distinct smoking and alcohol-associated methylation signatures, with specific CpG sites showing significant differential methylation compared to non-exposed patients. Our analysis provides insights into methylation profiles as predictive markers for distinguishing between BPH, PCa and mCRPC that are also influenced by lifestyle factors. More importantly, aberrations in methylation favor PCa aggressiveness to metastasis and genomic instability that implies aging and environmental factors. Overall, the differential methylation patterns suggest potential for patient stratification, biomarker-driven treatment strategies including epigenetic therapeutic strategies for AA PCa.
2026-03-30 | GSE323379 | GEO
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