Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany.
Department of Gynecology and Obstetrics, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany.
Life Sci. 2021 Jun 1;274:119345. doi: 10.1016/j.lfs.2021.119345. Epub 2021 Mar 10.
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.
临床研究表明，癌症患者的全身血管生物学发生改变。我们评估了有和无卵巢癌（OC）患者的肿瘤及肿瘤周围无组织中与内皮激活和血管渗漏相关的基因的表达模式。
本前瞻性观察性研究纳入了 10 例因妇科良性疾病诊断和 22 例晚期 OC 而计划接受剖腹术的患者。患者术前采集血清样本，从外周腹壁肌肉、无肿瘤的腹膜和肿瘤本身采集组织样本。
OC 组患者术中每时间单位接受的液体量明显更多（p=0.01）。基线时，OC 患者血清中白细胞介素 8（IL-8）和单核细胞趋化蛋白 1/CC 趋化因子配体 2（MCP-1/CCL2）、血管细胞黏附分子 1（VCAM-1，CD106）和细胞间黏附分子 1（ICAM-1，CD54）以及血栓调节蛋白明显升高（p=0.03）。OC 患者肿瘤组织中特定血管渗漏相关基因（血管生成素 1（ANG-1）、ANG-2、TIE2、VEGFR1、VEGFR2）的表达明显改变（p=0.003），而在无肿瘤的腹膜组织中，OC 组的 ANG-2/1 表达比值增加了一倍以上（p=0.03）。在外周肌肉中，OC 患者的 ANG/TIE 轴中的基因尤其发生了明显改变（p=0.005），提示存在与血管渗漏相关的特定基因型。OC 患者的基因表达变化与术后液体平衡明显相关（p=0.03）。
不仅在肿瘤中，而且在癌症患者的外周组织中，均检测到与屏障功能障碍和血管生成相关的基因的 ANG/TIE 轴表达改变。这可能导致与全身血管渗漏相关的特定基因型。
