Dataset Information

Decrease and gain of gene expression are equally discriminatory markers for prostate carcinoma: a gene expression analysis on total and microdissected prostate tissue.

ABSTRACT: Information on over- and underexpressed genes in prostate cancer in comparison to adjacent normal tissue was sought by DNA microarray analysis. Approximately 12,600 mRNA sequences were analyzed from a total of 26 tissue samples (17 untreated prostate cancers, 9 normal adjacent to prostate cancer tissues) obtained by prostatectomy. Hierarchical clustering was performed. Expression levels of 63 genes were found significantly (at least 2.5-fold) increased, whereas expression of 153 genes was decreased (at least 2.5-fold) in prostate cancer versus adjacent normal tissue. In addition to previously described genes such as hepsin, overexpression of several genes was found that has not drawn attention before, such as the genes encoding the specific granule protein (SGP28), alpha-methyl-acyl-CoA racemase, low density lipoprotein (LDL)-phospholipase A2, and the anti-apoptotic gene PYCR1. The radiosensitivity gene ATDC and the genes encoding the DNA-binding protein inhibitor ID1 and the phospholipase inhibitor uteroglobin were significantly down-regulated in the cancer samples. DNA microarray data for eight genes were confirmed quantitatively in five normal and five cancer tissues by real-time reverse transcriptase-polymerase chain reaction with a high correlation between the two methods. Laser capture microdissection of epithelial and stromal compartments from cancer and histological normal specimens followed by an amplification protocol for low levels of RNA (<0.1 microg) allowed us to distinguish between gene expression profiles characteristic of epithelial cells and those typical of stroma. Most of the genes identified in the nonmicrodissected tumor material as up-regulated were indeed overexpressed in cancerous epithelium rather than in the stromal compartment. We conclude that development of prostate cancer is associated with down-regulation as well as up-regulation of genes that show complex differential regulation in epithelia and stroma. Some of the gene expression alterations identified in this study may prove useful in the development of novel diagnostic and therapeutic strategies.

SUBMITTER: Ernst T

PROVIDER: S-EPMC1850818 | biostudies-literature | 2002 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Decrease and gain of gene expression are equally discriminatory markers for prostate carcinoma: a gene expression analysis on total and microdissected prostate tissue.

Ernst Thomas T Hergenhahn Manfred M Kenzelmann Marc M Cohen Clemens D CD Bonrouhi Mahnaz M Weninger Annette A Klären Ralf R Gröne Elisabeth F EF Wiesel Manfred M Güdemann Christof C Küster Jens J Schott Winfried W Staehler Gerd G Kretzler Matthias M Hollstein Monica M Gröne Hermann-Josef HJ

The American journal of pathology 20020601 6

Information on over- and underexpressed genes in prostate cancer in comparison to adjacent normal tissue was sought by DNA microarray analysis. Approximately 12,600 mRNA sequences were analyzed from a total of 26 tissue samples (17 untreated prostate cancers, 9 normal adjacent to prostate cancer tissues) obtained by prostatectomy. Hierarchical clustering was performed. Expression levels of 63 genes were found significantly (at least 2.5-fold) increased, whereas expression of 153 genes was decrea ...[more]

PMID: 12057920

Similar Datasets

Project description:BackgroundTumorigenesis is characterised by changes in transcriptional control. Extensive transcript expression data have been acquired over the last decade and used to classify prostate cancers. Prostate cancer is, however, a heterogeneous multifocal cancer and this poses challenges in identifying robust transcript biomarkers.MethodsIn this study, we have undertaken a meta-analysis of publicly available transcriptomic data spanning datasets and technologies from the last decade and encompassing laser capture microdissected and macrodissected sample sets.ResultsWe identified a 33 gene signature that can discriminate between benign tissue controls and localised prostate cancers irrespective of detection platform or dissection status. These genes were significantly overexpressed in localised prostate cancer versus benign tissue in at least three datasets within the Oncomine Compendium of Expression Array Data. In addition, they were also overexpressed in a recent exon-array dataset as well a prostate cancer RNA-seq dataset generated as part of the The Cancer Genomics Atlas (TCGA) initiative. Biologically, glycosylation was the single enriched process associated with this 33 gene signature, encompassing four glycosylating enzymes. We went on to evaluate the performance of this signature against three individual markers of prostate cancer, v-ets avian erythroblastosis virus E26 oncogene homolog (ERG) expression, prostate specific antigen (PSA) expression and androgen receptor (AR) expression in an additional independent dataset. Our signature had greater discriminatory power than these markers both for localised cancer and metastatic disease relative to benign tissue, or in the case of metastasis, also localised prostate cancer.ConclusionIn conclusion, robust transcript biomarkers are present within datasets assembled over many years and cohorts and our study provides both examples and a strategy for refining and comparing datasets to obtain additional markers as more data are generated.

Project description:BACKGROUND AND AIMS:Colorectal epithelial cells are prone to malignant transformation. Therefore, identification of differences in gene expression in the process from normal colonic crypts to adenomas with low grade dysplasia is essential for further insights into early tumorigenesis. To achieve this goal, a novel gene expression analysis strategy, screening for expressed transcripts in small histologically defined tissue samples, was performed. METHODS:First, laser mediated microdissection was used to isolate normal and adenomatous crypts from colonic cryosections. Then, nested RNA arbitrarily primed polymerase chain reaction (RAP-PCR) for differential display was performed to screen mRNA populations and to generate hybridisation probes for cDNA expression arrays. After evaluation of cDNA expression arrays, differential expression was confirmed at the protein level by immunohistochemistry. RESULTS:Evaluation of gene expression profiles of normal versus adenomatous colonic crypts of six different patients revealed, in general, dysregulation of up to 11% of all analysed genes (total number n=588): specifically, p21-rac1 was upregulated in four of six patients, mitogen activated protein kinase (MAPK) p38alpha in three of six patients, and interferon gamma receptor in three of six patients. Conversely, FAST kinase was found to be downregulated in three of six patients, p53 in three of six patients, and thrombospondin 2 in three of six patients. CONCLUSIONS:For the first time, distinct gene expression profiles of dysplastic areas within colonic adenomas, using the combination of laser mediated microdissection with RAP-PCR and cDNA expression array, were shown. In these samples, upregulation of proliferation associated genes (ras-oncogene related p21-rac1 and MAPK p38alpha) as well as downregulation of apoptosis related genes (FAST kinase and p53) most likely reflects specific alterations in adenomas with low grade dysplasia. Based on upregulation of p21-rac1 and MAPK p38alpha, activation of the MAPK pathway appears to be an early event in colonic carcinogenesis.

Dataset Information

Decrease and gain of gene expression are equally discriminatory markers for prostate carcinoma: a gene expression analysis on total and microdissected prostate tissue.

Publications

Decrease and gain of gene expression are equally discriminatory markers for prostate carcinoma: a gene expression analysis on total and microdissected prostate tissue.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets