Large-Scale Serial Analysis of Gene Expression Reveals Genes Differentially Expressed in Ovarian Cancer
2000
Difficulties in the detection, diagnosis, and treatment of ovarian
cancer result 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 used serial analysis of gene expression
(SAGE) to generate global gene expression profiles from various
ovarian cell lines and tissues, including primary cancers, ovarian
surface epithelia cells, and cystadenoma cells. The profiles were used
to compare overall patterns of gene expression and to identify
differentially expressed genes. We have sequenced a total of 385,000
tags, yielding >56,000 genes expressed in 10 different libraries
derived from ovarian tissues. In general, ovarian cancer cell lines
showed relatively high levels of similarity to libraries from other
cancer cell lines, regardless of the tissue of origin (ovarian or
colon), indicating that these lines had lost many of their
tissue-specific expression patterns. In contrast, immortalized ovarian
surface epithelia and ovarian cystadenoma cells showed much higher
similarity to primary ovarian carcinomas than to primary colon
carcinomas. Primary tissue specimens therefore appeared to be a
better model for gene expression analyses. Using the expression
profiles described above and stringent selection criteria, we have
identified a number of genes highly differentially expressed between
nontransformed ovarian epithelia and ovarian carcinomas. Some of the
genes identified are already known to be overexpressed 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-1, epithelial cellular adhesion
molecule, and mesothelin. Interestingly, both apolipoprotein E
(ApoE) and ApoJ, two proteins involved in lipid homeostasis, are among
the genes highly up-regulated in ovarian cancer. Selected serial
analysis of gene expression results were further validated through
immunohistochemical analysis of ApoJ, claudin-3, claudin-4, and
epithelial cellular adhesion molecule in archival material. These
experiments provided additional evidence of the relevance of our
findings in vivo . The publicly available expression data
reported here should stimulate and aid further research in the field of
ovarian cancer.
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