Abstract
BackgroundOvarian cancer is the most deadly gynecological cancer due to late diagnosis at advanced stage with major peritoneal involvement. To date most research has focused on primary tumor. However the prognosis is directly related to residual disease at the end of the treatment. Therefore it is mandatory to focus and study the biology of meatastatic disease that is most frequently localized to the peritoneal caivty in ovarian cancer.MethodsWe used high-density gene expression arrays to investigate gene expression changes between matched primary and metastatic (peritoneal) lesions.ResultsHere we show that gene expression profiles in peritoneal metastasis are significantly different than their matched primary tumor and these changes are affected by underlying copy number variation differences among other causes. We show that differentially expressed genes are enriched in specific pathways including JAK/STAT pathway, cytokine signaling and other immune related pathways. We show that underlying copy number variations significantly affect gene expression. Indeed patients with important differences in copy number variation displayed greater gene expression differences between their primary and matched metastatic lesions.ConclusionsOur analysis shows a very specific targeting at both the genomic and transcriptomic level to upregulate certain pathways in the peritoneal metastasis of ovarian cancer. Moreover, while primary tumors use certain pathways we identify distinct differences with metastatic lesions. The variation between primary and metastatic lesions should be considered in personalized treatment of ovarian cancer.
Highlights
Ovarian cancer is the most deadly gynecological cancer due to late diagnosis at advanced stage with major peritoneal involvement
It is clear from our results that specific pathways in the peritoneum have both been selected for over-expression and amplification with respect to the primary tumor
It is likely that the increased gene expression of these pathways is critical to survival in the microenvironment as Wang and colleagues showed that similar pathways are upregulated in normal peritoneum of patients with ovarian cancer versus those with benign conditions [16]
Summary
Ovarian cancer is the most deadly gynecological cancer due to late diagnosis at advanced stage with major peritoneal involvement. With the advent of personalized medicine it is critical to understand the molecular pathways underlying peritoneal metastasis in order to be able to define new therapeutic strategies. This will require understanding the genetic variation in both primary and metastatic lesions to correctly optimize the therapy on an individual basis. Lancaster et al have compared primary ovarian tumor and omental metastatic lesions in a study of 20 patients. The genes uncovered by their approach were previously implicated in the metastatic process, cell motility, migration, and cytoskeletal function Critical networks such as the p53 pathway were enriched [9]
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