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

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). Patients being schedul...

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Bibliographic Details
Published in:Life sciences (1973) 2021-06, Vol.274, p.119345, Article 119345
Main Authors: Kinnen, Alexander, Klaschik, Sven, Neumann, Claudia, Egger, Eva-Katharina, Mustea, Alexander, Soehle, Martin, Frede, Stilla, Velten, Markus, Coburn, Mark, Hilbert, Tobias
Format: Article
Language:English
Subjects:
Abdominal wall
Angiogenesis
Angiopoietin
Angiopoietin-1 - genetics
Angiopoietin-1 - metabolism
Angiopoietin-2 - genetics
Angiopoietin-2 - metabolism
Angiopoietins
Biomarkers, Tumor - genetics
Biomarkers, Tumor - metabolism
Cancer
Carcinogenesis
Female
Gene expression
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Genes
Genotypes
Humans
Intercellular adhesion molecule 1
Interleukin 8
Leakage
Monocyte chemoattractant protein 1
Observational studies
Ovarian cancer
Ovarian Neoplasms - genetics
Ovarian Neoplasms - metabolism
Ovarian Neoplasms - pathology
Peritoneum
Peritoneum - metabolism
Prognosis
Prospective Studies
Receptor, TIE-2 - genetics
Receptor, TIE-2 - metabolism
Thrombomodulin
Tissues
Tumors
Vascular cell adhesion molecule 1
Vascular Endothelial Growth Factor Receptor-1 - genetics
Vascular Endothelial Growth Factor Receptor-1 - metabolism
Vascular Endothelial Growth Factor Receptor-2 - genetics
Vascular Endothelial Growth Factor Receptor-2 - metabolism
Vascular leakage
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Summary: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). 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. 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). 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.
ISSN:0024-3205
1879-0631
DOI:10.1016/j.lfs.2021.119345