Transcriptome-wide gene expression analysis of prostate cancer (PCa) needle biopsies
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE134171 | GEO | 2020/07/21
REPOSITORIES: GEO
Similar Datasets
Project description:We assessed transcriptome-wide gene expression in tissue specimens of PCa patients who underwent radical prostatectomy (RP) by next-generation sequencing (HiSeq 2500). We applied Cox proportional hazard models to the cohorts from different platforms and specimen types and combined the evidence from these by fixed effect meta-analysis to identify genes predictive for time to DoD (death of disease). Genes were combined by a weighted median approach into a prognostic score. 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). 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).
2020-07-21 | GSE134170 | GEO
Project description:We assessed transcriptome-wide gene expression in tissue specimens of PCa patients who underwent radical prostatectomy by next-generation sequencing (HiSeq 2000). We applied Cox proportional hazard models to the cohorts from different platforms and specimen types and combined the evidence from these by fixed effect meta-analysis to identify genes predictive for time to DoD (death of disease). Genes were combined by a weighted median approach into a prognostic score. 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). 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.
2020-07-21 | GSE134168 | GEO
Project description:We assessed transcriptome-wide gene expression in tissue specimens of PCa patients who underwent radical prostatectomy by a custom expression microarray. We applied Cox proportional hazard models to the cohorts from different platforms and specimen types and combined the evidence from these by fixed effect meta-analysis to identify genes predictive for time to DoD (death of disease). Genes were combined by a weighted median approach into a prognostic score. 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). 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.
2020-07-21 | GSE134160 | GEO
Project description:Molecular and genomic analysis of microscopic quantities of tumor from formalin-fixed and paraffin-embedded (FFPE) biopsies has many unique challenges. Here we evaluated the feasibility of obtaining transcriptome-wide RNA expression to measure prognostic classifiers from diagnostic prostate needle core biopsies. 158 samples from diagnostic needle core biopsies (Bx) and radical prostatectomies (RP) were collected from 33 patients at three hospitals, each patient provided up to 6 tumor and benign samples. Genome-wide transcriptomic profiles were generated using Affymetrix Human Exon arrays for comparison of gene expression alterations and prognostic signatures between the Bx and RP samples. For 23 patients from UCSF and CSMC, six prostate tissue samples were obtained from each patient: tumor biopsy, tumor RP, benign adjacent biopsy, benign adjacent RP, and benign contralateral biopsy, and benign contralateral RP. For the 10 UHN patients only tumor biopsy and tumor RP samples were obtained. A total of 147 samples passed RNA, cDNA, and microarray quality control.
2016-03-09 | E-GEOD-72220 | biostudies-arrayexpress
Project description:The dataset consists of 266 NCCN very low/low or favorable-intermediate risk PCa patients who underwent diagnostic prostate biopsy between 2000 and 2014 and were treated with RP in six community or academic practices: University of Calgary, Cedars-Sinai, Spectrum Health, Cleveland Clinic, MD Anderson Cancer Center and Johns Hopkins. All patients had complete tumor pathology from biopsy and prostatectomy. Low risk PCa was defined as T1c or cT2a, and Gleason score (GS) ≤ 6, and PSA < 10ng/ml and favorable-intermediate risk was no greater than predominant GS 3 and percent positive biopsy cores < 50%, and either cT2b-cT2c or PSA 10-20ng/ml.
2018-09-08 | GSE119616 | GEO
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:Genome wide DNA methylation profiling of brochoscopic paired biopsy samples from tumoral sites and the contralateral bronchus (controls). The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 450,000 CpGs in bronchoscopic biopsy samples. In 37 patients (74 samples) a difinite histological diagnosis could be reached. In the remaining 36 samples the diagnosis remained indefinite, the assumption of the pathologists is stated.
2021-03-02 | GSE158075 | GEO
Project description:Here we present a dataset from 84 DGC patients with paired tumor and nearby tissue. Tumors and their nearby tissues were evaluated by pathologists. Nearby tissues were designated as non-cancerous and were greater than 5 cm away from the surgery margin. Hematoxylin and eosin (H&E) stained sections were examined by two expert gastrointestinal pathologists (Z.L. and Yumei Lai) independently to confirm: (1) diffuse type (Lauren type); (2) >50% tumor cell nuclei; (3) <20% necrosis in tumor tissue; (4) no tumor cells in nearby tissue.
2018-02-09 | PXD008840 | Pride
Project description:Histologic diagnosis of T cell-mediated rejection in kidney transplant biopsies has limited reproducibility because it is based on non-specific lesions using arbitrary rules that are subject to differing interpretations. We used microarray results from 403 indication biopsies previously given histologic diagnoses to develop a molecular classifier that assigned a molecular T cell-mediated rejection score to each biopsy. Independent assessment of the biopsies by multiple pathologists confirmed considerable disagreement on the presence of TCMR features: 79-88% accuracy and 35-69% sensitivity. The agreement of the molecular T cell-mediated rejection score with the histology diagnosis was similar to agreement among individual pathologists: accuracy 89%, sensitivity 51%. However, the score also predicted the consensus among pathologists, being highest when all agreed. Many discrepancies between the scores and the histologic diagnoses were in situations where histology is unreliable e.g. scarred biopsies. The score correlated with histologic lesions and gene sets associated with T cell-mediated rejection. The transcripts most often selected by the classifier were expressed in effector T cells, dendritic cells, or macrophages or inducible by interferon-gamma. Thus the T cell-mediated rejection score offers an objective assessment of kidney transplant biopsies, predicting the consensus opinion among multiple pathologists, and offering insights into underlying disease mechanisms. Antibody-mediated rejection is a major cause of kidney transplant failure, but the current diagnostic system misses most cases due to dependency on subjective non-standardized tests. We hypothesized that molecular features could provide a test to address this problem. We classified 403 biopsies by a reference standard based on microcirculation lesions and donor-specific HLA antibody, and used microarray analysis to develop a classifier that assigned each biopsy a score reflecting the probability of antibody-mediated rejection. The scores correlated with donor-specific antibody and histologic lesions: 42/45 biopsies with antibody-mediated rejection scores >0.5 had both donor-specific antibody and microcirculation lesions. Intermediate scores (0.2-0.5) were more ambiguous, but became more specific combined with donor-specific antibody. Compared to diagnoses based on histology-plus-donor-specific antibody, the scores had sensitivity 0.67; specificity 0.90. Donor-specific antibody improved the specificity to 0.97. The score correlated not only with diagnoses of individual pathologists but with the consensus among multiple pathologists. The classifier used transcripts expressed in endothelial cells (e.g. CDH13, DARC, ROBO4) and NK cells (e.g. CX3CR1, FGFBP2), as well as IFNG-inducible transcripts e.g. CXCL11. Thus the molecular phenotype of antibody-mediated rejection provides not only an objective test that predicts microcirculation lesions and donor-specific HLA antibody, but also offers mechanistic insights.
2013-02-13 | GSE36059 | 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