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Integrative molecular concept modeling of prostate cancer progression
- Source :
- Nature Genetics. 39:41-51
- Publication Year :
- 2006
- Publisher :
- Springer Science and Business Media LLC, 2006.
-
Abstract
- Despite efforts to profile prostate cancer, the genetic alterations and biological processes that correlate with the observed histological progression are unclear. Using laser-capture microdissection to isolate 101 cell populations, we have profiled prostate cancer progression from benign epithelium to metastatic disease. By analyzing expression signatures in the context of over 14,000 'molecular concepts', or sets of biologically connected genes, we generated an integrative model of progression. Molecular concepts that demarcate critical transitions in progression include protein biosynthesis, E26 transformation-specific (ETS) family transcriptional targets, androgen signaling and cell proliferation. Of note, relative to low-grade prostate cancer (Gleason pattern 3), high-grade cancer (Gleason pattern 4) shows an attenuated androgen signaling signature, similar to metastatic prostate cancer, which may reflect dedifferentiation and explain the clinical association of grade with prognosis. Taken together, these data show that analyzing gene expression signatures in the context of a compendium of molecular concepts is useful in understanding cancer biology.
- Subjects :
- Male
medicine.medical_specialty
medicine.drug_class
Prostatic Hyperplasia
Context (language use)
Disease
Biology
Prostate cancer
Internal medicine
Genetics
medicine
Humans
Neoplasm Metastasis
Microdissection
Prostatic Intraepithelial Neoplasia
Gene Expression Profiling
Prostatic Neoplasms
Cancer
Models, Theoretical
medicine.disease
Androgen
Systems Integration
Gene expression profiling
Endocrinology
Tumor progression
Androgens
Disease Progression
Cancer research
Signal Transduction
Subjects
Details
- ISSN :
- 15461718 and 10614036
- Volume :
- 39
- Database :
- OpenAIRE
- Journal :
- Nature Genetics
- Accession number :
- edsair.doi.dedup.....0a41fd85314d0662b59a21577f07cc3f