Gene expression analysis of matched ovarian primary tumors and peritoneal metastasis

作者：Malek Joel A; Martinez Alejandra; Mery Eliane; Ferron Gwenael; Huang Ruby; Raynaud Christophe; Jouve Eva; Thiery Jean Paul; Querleu Denis; Rafii Arash^*

来源：Journal of Translational Medicine, 2012, 10: 121.

DOI：10.1186/1479-5876-10-121

Background: Ovarian 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.
Methods: We used high-density gene expression arrays to investigate gene expression changes between matched primary and metastatic (peritoneal) lesions.
Results: Here 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.
Conclusions: Our 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.

• 出版日期2012-6-11