Gene expression in the Angiopoietin/TIE axis is altered in peripheral tissue of ovarian cancer patients: A prospective observational study.

AIMS: Clinical studies suggest altered systemic vascular biology in cancer patients. We assessed expression patterns of endothelial activation- and vascular leakage-related genes in tumor as well as in tumor-free peripheral tissues from patients with and without ovarian cancer (OC). MAIN METHODS: Patients being scheduled for laparotomy for either gynecologic benign diagnosis (n = 10) or for advanced-stage OC (n = 22) were prospectively recruited to this observational study. Serum samples were taken preoperatively, and tissue samples were taken from peripheral abdominal wall musculature, tumor-free peritoneum and the tumor itself. KEY FINDINGS: Patients in OC group received significantly more fluid per time intraoperatively (p = 0.01). IL-8 and MCP-1/CCL2, VCAM-1 (CD 106) and ICAM-1 (CD 54) as well as Thrombomodulin were significantly increased in cancer patients' serum at baseline (p = 0.03). Expression of distinct vascular leakage-related genes (Angiopoietin-1 (ANG-1), ANG-2, TIE2, VEGFR1, VEGFR2) was significantly altered in tumor tissue of OC patients (p = 0.003), while in tumor-free peritoneal tissue, ANG-2/1 expression ratio was more than doubled in OC group (p = 0.03). In peripheral musculature, particularly genes from the ANG/TIE axis were significantly changed in OC patients (p = 0.005), suggesting a distinct vascular leakage-related genotype. Gene expression changes in OC patients were significantly associated with the postoperative fluid balance (p = 0.03). SIGNIFICANCE: Altered expression of barrier dysfunction- and angiogenesis-associated genes from the ANG/TIE axis was detected not only in tumor but also in peripheral tissues of cancer patients. This may contribute to a systemic vascular leakage-related genotype.