Gene expression analysis of matched ovarian primary tumors and peritoneal metastasis.
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 metastatic disease that is most frequently localized to the peritoneal cavity 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.
Genomics Core, Weill Cornell Medical College in Qatar, Education city, Qatar Foundation, Doha, Qatar PO 241 44.
Joel A
JA
Malek
Alejandra
A
Martinez
Eliane
E
Mery
Gwenael
G
Ferron
Ruby
R
Huang
Christophe
C
Raynaud
Eva
E
Jouve
Jean-Paul
JP
Thiery
Denis
D
Querleu
Arash
A
Rafii
D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000235:genetics / Q000556:secondary*; D011379:Prognosis