Large-scale serial analysis of gene expression reveals genes differentially expressed in ovarian cancer

Difficulties in the detection, diagnosis, and treatment of ovarian cancer r esult in an overall low survival rate of women with this disease. A better understanding of the pathways involved in ovarian tumorigenesis will likely provide new targets for early and effective intervention. Here, we have us ed serial analysis of gene expression (SAGE) to generate global gene expres sion profiles from various ovarian cell lines and tissues, including primar y cancers, ovarian surface epithelia cells, and cystadenoma cells. The prof iles were used to compare overall patterns of gene expression and to identi fy differentially expressed genes. We have sequenced a total of 385,000 tag s, yielding 256,000 genes expressed in 10 different Libraries derived from ovarian tissues. In general, ovarian cancer cell Lines showed relatively hi gh levels of similarity to libraries from other cancer felt lines, regardle ss of the tissue of origin (ovarian or colon), indicating that these lines had lost many of their tissue-specific expression patterns, In contrast, im mortalized ovarian surface epithelia and ovarian cystadenoma cells showed m uch higher similarity to primary ovarian carcinomas than to primary colon c arcinomas. Primary tissue specimens therefore appeared to be a better model for gene expression analyses. Using the expression profiles described abov e and stringent selection criteria, we have identified a number of genes hi ghly differentially expressed between nontransformed ovarian epithelia and ovarian carcinomas. Some of the genes Identified are already known to be ov erexpressed in ovarian cancer, but several represent novel candidates. Many of the genes up-regulated in ovarian cancer represent surface or secreted proteins such as claudin-3 and -4, HE4, mucin-l, epithelial cellular adhesi on molecule, and mesothelin, Interestingly, both apolipoprotein E (ApoE) an d ApoJ, two proteins involved in lipid homeostasis, are among the genes hig hly up-regulated in ovarian cancer, Selected serial analysis of gene expres sion results were further validated through immunohistochemical analysis of ApoJ, claudin-3, claudin-4, and epithelial cellular adhesion molecule in a rchival material. These experiments provided additional evidence of the rel evance of our findings in vivo. The publicly available expression data repo rted here should stimulate and aid further research in the field of ovarian cancer.