Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Androgen Regulated Genes in Intact Human Prostate Tissues: Relation to Benign Prostatic Hyperplasia and Prostate Cancer

ABSTRACT: To investigate gene expression profiling in intact human prostate tissue xenografts in mice, following the addition or subtraction of androgens. 58 prostate samples were implanted into castrated or testosterone-treated mice for 5 different lengths of time. Samples were compared to a control pool created by combining day zero tissue samples from all patients

ORGANISM(S): Homo sapiens

SUBMITTER: Simon Hayward

PROVIDER: E-GEOD-17862 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Androgen regulated genes in human prostate xenografts in mice: relation to BPH and prostate cancer.

Love Harold D HD Booton S Erin SE Boone Braden E BE Breyer Joan P JP Koyama Tatsuki T Revelo Monica P MP Shappell Scott B SB Smith Jeffrey R JR Hayward Simon W SW

PloS one 20091221 12

Benign prostatic hyperplasia (BPH) and prostate carcinoma (CaP) are linked to aging and the presence of androgens, suggesting that androgen regulated genes play a major role in these common diseases. Androgen regulation of prostate growth and development depends on the presence of intact epithelial-stromal interactions. Further, the prostatic stroma is implicated in BPH. This suggests that epithelial cell lines are inadequate to identify androgen regulated genes that could contribute to BPH and ...[more]

PMID: 20027305

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Project description:The ability to interrogate circulating tumor cells (CTC) and disseminated tumor cells (DTC) is restricted by the small number detected and isolated (typically <10). We wanted to determine if a commercially available technology could provide a transcriptomic profile of a single prostate cancer (PCa) cell. We clonally selected and cultured a single passage of cell cycle synchronized C4-2B PCa cells. Ten sets of single, 5-, or 10-cells were isolated using a micromanipulator under direct visualization with an inverted microscope. Additionally, we analyzed 10 individual DTC isolated from each of 2 patients with metastatic PCa. We have shown that a transcriptomic profile can be obtained from a single cell using commercially available technology. As expected, fewer amplified genes are detected from a single-cell sample than from pooled cell samples, but this method can be used to obtain a transcriptomic profile from DTC isolated from the bone marrow of patients with PCa. Custom Agilent 44K whole human genome expression oligonucleotide microarrays were used to profile clonally selected and cultured single passage of cell cycle synchronized C4-2B PCa cells isolated using a micromanipulator under direct visualization with an inverted microscope into ten sets of single, 5-, or 10-cells. Single disseminated tumor cells were isolated from bone marrow (BM) samples of two advanced prostate cancer patients. Essentially, a two-step selection process was employed, in which anti-CD45 and anti-CD61 conjugated to immunomagnetic beads were used for negative selection, and anti-HEA was used for positive selection. Cells were then fluorescently stained for BerEP4, counter stained with RPE anti-CD45, and individually selected (10 single cells each per patient) under fluorescent light using a micropipette system for further analysis. RNA was amplified using the WT-Oviation one-direct system and hybridization against a common reference pool of prostate tumor cell lines. Data from C42B cell data and data from single cells isolated from the bone marrow of patients were normalized and analyzed separately.

Project description:After therapy for prostate cancer many men develop a rising PSA. Such men may develop a local or metastatic recurrence that warrants further therapy. However many men will have no evidence of disease progression other than the rising PSA and will have a good outcome. A case-control design, incorporating test and validation cohorts, was used to test the association of gene expression results with outcome after PSA recurrence. Since clinical training and validation analysis requires tissue from patients with sufficient follow-up time, for this study we sampled individuals from the Mayo Radical Retropubic Prostatectomy (RRP) Registry. The registry consists of a population of men who received prostatectomy as their first treatment for prostate cancer at the Mayo Clinic (For a current description and use of the registry; see PMID: 17418069). As systemic progression is relatively infrequent, we designed a case-control study nested within a cohort of men with a rising PSA. Between 1987-2001, inclusive, 9,989 previously-untreated men had RRP at Mayo. On follow-up, 2,131 developed a rising PSA (>30 days after RRP) in the absence of concurrent clinical recurrence. PSA rise was defined as a follow-up PSA >= 0.20 ng/ml, with the next PSA at least 0.05 ng/ml higher or the initiation of treatment for PSA recurrence (for patients whose follow-up PSA was high enough to warrant treatment). This group of 2,131 men comprises the underlying cohort from which SYS cases and PSA controls were selected. Within 5 years of PSA rise, 213 men developed systemic progression (SYS cases), defined as a positive bone scan or CT scan. Of these, 100 men succumbed to a prostate cancer-specific death, 37 died from other causes and 76 remain at risk. PSA recurrence controls (213) were selected from those men without systemic progression within 5 years after the PSA rise and were matched (1:1) on birth year, calendar year of PSA rise and initial diagnostic pathologic Gleason score (<=6, 7+). Twenty of these men developed systemic progression greater than 5 years after initial PSA rise and 9 succumbed to a prostate cancer-specific death. A set of 213 No Evidence of Disease (NED) Progression controls were also selected from the Mayo RRP Registry of 9,989 men and used for some comparisons. These controls had RRP from 1987-1998 with no evidence of PSA rise within 7 years of RRP. The median (25th, 75th percentile) follow-up from RRP was 11.3 (9.3, 13.8) years. The NED controls were matched to the systemic progression cases on birth-year, calendar year of RRP and initial diagnostic Gleason Score. Computerized optimal matching was performed to minimize the total distance between cases and controls in terms of the sum of the absolute difference in the matching factors (PMID: 8728456). All paraffin-embedded blocks from eligible men were identified and each block was surveyed for the tissue present (primary and secondary Gleason cancer regions, normal and metastatic lymph nodes, etc.). Of the 639 eligible patients, paraffin blocks were available on 623 (97.5%). Similarly, RNA was successfully isolated and the DASL assays successfully performed on a very high proportion of patients/specimens: Usable RNA was prepared from all 623 blocks, and the Cancer Panel and custom prostate cancer panel DASL arrays were both successful on 596 RNA specimens (95.7% of RNAs; 93.3% of design patients). Keywords: outcome prediction 596 total cases (n=200, 201, 195 for systemic disease progression, PSA recurrence and no evidence of disease groups).

Dataset Information

Androgen Regulated Genes in Intact Human Prostate Tissues: Relation to Benign Prostatic Hyperplasia and Prostate Cancer

Publications

Androgen regulated genes in human prostate xenografts in mice: relation to BPH and prostate cancer.

Similar Datasets

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