Coordinately up-regulated genes in ovarian cancer

A better understanding of the molecular circuitry in normal ovarian tissues and in ovarian cancer will likely provide new targets for diagnosis and th erapy. Recently, much has been learned about the genes expressed in ovarian cancer through studies with cDNA arrays and serial analysis of gene expres sion, However, these methods do not allow highly quantitative analysis of g ene expression on a large number of specimens. Here, we have used quantitat ive real-time RT-FCR in a panel of 39 microdissected ovarian carcinomas of various subtypes to systematically analyze the expression of 13 genes, many of which were previously identified as up-regulated in a subset of ovarian cancers by serial analyses of gene expression. The genes analyzed are glut athione peroxidase 3 (GPX3), apolipoprotein J/clusterin, insulin-like growt h factor-binding protein 2, epithelial cell adhesion molecule/GA733-2, Kop protease inhibitor, matrix gla protein, tissue inhibitor of metalloproteina se 3, folate receptor 1, S100A2, signal transducer and activator of transcr iption 1, secretory leukocyte protease inhibitor, apolipoprotein E, and cer uloplasmin. All of the genes were found overexpressed, some at extremely hi gh levels, in the vast majority of ovarian carcinomas irrespective of the s ubtype. Interestingly, GPX3 was found at much higher levels in tumors with clear cell histology and may represent a biomarker for this subtype. Some o f the genes studied here may thus represent targets for early detection ova rian cancer. The gene expression patterns were not associated with age at d iagnosis, stage, or K-ras mutation status in ovarian cancer. We find that s everal genes are coordinately regulated in ovarian cancer, likely represent ing the fact that many genes are activated as part of common signaling path ways or that extensive cross-talk exists between several pathways in ovaria n cancer, A statistical analysis shows that genes commonly upregulated in o varian cancer may result from the aberrant activation of a limited number o f pathways, providing promising targets for novel therapeutic strategies.