Identification of genes associated with ovarian cancer metastasis using microarray expression analysis

Abstract

Although the transition from early- to advanced-stage ovarian cancer is a critical determinant of survival, little is known about the molecular underpinnings of ovarian metastasis. We hypothesize that microarray analysis of global gene expression patterns in primary ovarian cancer and metastatic omental implants can identify genes that underlie the metastatic process in epithelial ovarian cancer. We utilized Affymetrix U95Av2 microarrays to characterize the molecular alterations that underlie omental metastasis from 47 epithelial ovarian cancer samples collected from multiple sites in 20 patients undergoing primary surgical cytoreduction for advanced-stage (IIIC/IV) serous ovarian cancer. Fifty-six genes demonstrated differential expression between ovarian and omental samples (P < 0.01), and twenty of these 56 differentially expressed genes have previously been implicated in metastasis, cell motility, or cytoskeletal function. Ten of the 56 genes are involved in p53 gene pathways. A Bayesian statistical tree analysis was used to identify a 27-gene expression pattern that could accurately predict the site of tumor (ovary versus omentum). This predictive model was evaluated using an external data set. Nine of the 27 predictive genes have previously been shown to be involved in oncogenesis and/or metastasis, and 10/27 genes have been implicated in p53 pathways. Microarray findings were validated by real-time quantitative PCR. We conclude that gene expression patterns that distinguish omental metastasis from primary epithelial ovarian cancer can be identified and that many of the genes have functions that are biologically consistent with a role in oncogenesis, metastasis, and p53 gene networks.

Treatment-Related Protein Biomarker Expression Differs between Primary and Recurrent Ovarian Carcinomas

“…In addition to the differences noted in recurrences compared with primary specimens, we found that expression of some of the markers (i.e., PGP as well as EGFR, BCRP, RRM1, and TOPO1) also differed in recurrent specimens taken from the same patient at different times during the course of disease. These differences may reflect alterations in gene expression programs that are dependent on the site of the tumor as suggested by genomic profiling studies of primary ovarian and omental lesions (22) or the genotypic divergence observed in multiple metastases derived from matched primary tumors obtained from untreated patients (23). In our study, the recurrences tested were obtained from patients who had received 1 to 5 prior therapies, so it is also possible that the chemotherapy regimen received in the intervening time period either induced/repressed expression of these proteins or selected for a preexisting tumor cell population with an altered expression of that marker.…”

Expressional Analyses of NM23-H1, KAI1 and MKK4 Metastasis-Related Genes in Metastatic Ovarian Carcinomas

“…However, differential expression of NM23-H1, KAI1 and MKK4 genes has not been reported in primary ovarian tumors compared to metastatic lesions of EOC in two recent global gene expression analyses. 17,18 On the other hand, metastasis suppressor roles of these three genes in ovarian cancer have been speculated by previous studies at the protein level. 7,12,15,19 A summary of the studies investigating the expression levels of NM23-H1, KAI1 and MKK4 genes in clinical samples are given in Table 3.…”

Poroceratose superficial disseminada num doente com colangiocarcinoma: manifestação paraneoplásica?

“…7,8 Recent studies have highlighted the importance of this gene in the oncogenesis of hepatocellular carcinoma, cholangiocarcinoma and ovarian adenocarcinoma. [9][10][11] Overexpression of the p53 gene in keratinocytes above and adjacent to the cornoid lamella in porokeratosis lesions has also been demonstrated, resulting in early apoptosis and abnormal differentiation of these cells. This finding suggests its involvement in the pathogenesis of these lesions.…”