Analysis of gene expression identifies candidate markers and pharmacological targets in prostate cancer.
Detection, treatment, and prediction of outcome for men with prostate cancer increasingly depend on a molecular understanding of tumor development and behavior. We characterized primary prostate cancer by monitoring expression levels of more than 8900 genes in normal and malignant tissues. Patterns of gene expression across tissues revealed a precise distinction between normal and tumor samples, and revealed a striking group of about 400 genes that were overexpressed in tumor tissues. We ranked these genes according to their differential expression in normal and cancer tissues by selecting for highly and specifically overexpressed genes in the majority of cancers with correspondingly low or absent expression in normal tissues. Several such genes were identified that act within a variety of biochemical pathways and encode secreted molecules with diagnostic potential, such as the secreted macrophage inhibitory cytokine, MIC-1. Other genes, such as fatty acid synthase, encode enzymes known as drug targets in other contexts, which suggests new therapeutic approaches.
Welsh
J B
JB
Genomics Institute of the Novartis Research Foundation, San Diego, California 92121, USA.
Sapinoso
L M
LM
Su
A I
AI
Kern
S G
SG
Wang-Rodriguez
J
J
Moskaluk
C A
CA
Frierson
H F
HF
Hampton
G M
GM
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D064429:Fatty Acid Synthases / Q000096:biosynthesis / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055436:Growth Differentiation Factor 15; D006801:Humans; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000096:biosynthesis / Q000235:genetics; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012697:Serine Endopeptidases / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D014408:Biomarkers, Tumor; D016207:Cytokines; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D064429:Fatty Acid Synthases; D012697:Serine Endopeptidases; C055645:hepsin; D017430:Prostate-Specific Antigen