Integrative microarray analysis of pathways dysregulated in metastatic prostate cancer.
Microarrays have been used to identify genes involved in cancer progression. We have now developed an algorithm that identifies dysregulated pathways from multiple expression array data sets without a priori definition of gene expression thresholds. Integrative microarray analysis of pathways (IMAP) was done using existing expression array data from localized and metastatic prostate cancer. Comparison of metastatic cancer and localized disease in multiple expression array profiling studies using the IMAP approach yielded a list of about 100 pathways that were significantly dysregulated (P < 0.05) in prostate cancer metastasis. The pathway that showed the most significant dysregulation, HIV-I NEF, was validated at both the transcript level and the protein level by quantitative PCR and immunohistochemical analysis, respectively. Validation by unsupervised analysis on an independent data set using the gene expression signature from the HIV-I NEF pathway verified the accuracy of our method. Our results indicate that this pathway is especially dysregulated in hormone-refractory prostate cancer.
Setlur
Sunita R
SR
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Royce
Thomas E
TE
Sboner
Andrea
A
Mosquera
Juan-Miguel
JM
Demichelis
Francesca
F
Hofer
Matthias D
MD
Mertz
Kirsten D
KD
Gerstein
Mark
M
Rubin
Mark A
MA
D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000502:physiology; D052002:NF-kappa B p50 Subunit / Q000502:physiology; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D015398:Signal Transduction / Q000502:physiology*; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000502:physiology
D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1