Stage-dependent angiopoietin-Tie2 and nitric oxide signaling of erythrocytes in response to surgical trauma in head and neck cancer
Background: Angiopoietin-Tie2 and nitric oxide pathway is crucial in tumor angiogenesis and closely correlates with tumor development, growth, and metastasis. This study aimed to investigate the angiopoietin-Tie2 and nitric oxide signaling of erythrocyte membrane in response to surgical trauma in head and neck cancer.Methods: We prospectively enrolled the patients with histology-proven head and neck squamous cell carcinoma undergoing surgical resection of primary tumors at the medical center
... e medical center between August and November 2019. We measured the preoperative and postoperative levels of angiopoietin-1, angiopoietin-2 in plasma using enzyme-linked immunosorbent assays, nitric oxide in plasma using nitrate/nitrite colorimetric assays, and Tie2 phosphorylation in erythrocyte membrane using Western blotting. Results: The plasma angiopoietin-1 was down-regulated from median 971.3 pg/mL (interquartile range [IQR]: 532.1 – 1569.3) to 417.9 (IQR: 270.5 – 597.3) after tumor resection (p=0.0020). Conversely, the plasma angiopoietin-2 was enhanced from 1173.6 pg/mL (IQR: 977.7 – 1450.2) to 2353.7 (IQR: 1352.4 – 2954.3) after surgery (p=0.0021), with a concomitant increase in plasma nitric oxide level from 7.73 μM (IQR: 5.39 – 10.06) to 10.50 (IQR: 7.65 – 14.18) after surgical resection (p=0.0093). Subgroup analyses further showed the angiopoietin-Tie2 and nitric oxide signaling was significant only in stage III and IV cancer.Conclusions: The dynamic change of angiopoietin-Tie2 signaling in erythrocyte membrane along with the enhanced nitric oxide in plasma after tumor resection suggests erythrocytes play a significant role in modulating surgery-induced angiogenesis, which may provide a novel marker for cancer surveillance and control.