Department of Gynecology and Breast Care Center, University Hospital, Charité Universitätsmedizin Berlin, Berlin, Germany.
Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Munich, Germany.
Sci Rep. 2020 Feb 27;10(1):3635. doi: 10.1038/s41598-020-59823-5.
The antiangiogenic splice variant VEGF-A165b is downregulated in a variety of cancer entities, but little is known so far about circulating plasma levels. The present analysis addresses this question and examines circulating VEGF-A/VEGF-A165b levels in a collective of female high-risk breast cancer patients over the course of treatment. Within the SUCCES-A trial 205 patients were recruited after having received primary breast surgery. Using ELISA VEGF-A/VEGF-A165b concentrations were determined and correlated to clinical characteristics (1) before adjuvant chemotherapy, (2) four weeks and (3) two years after therapy and compared to healthy controls (n = 107). VEGF levels were significantly elevated after completion of chemotherapy. Within the breast cancer cohort, VEGF-A165b levels increased two years after completion of chemotherapy. VEGF-A plasma concentrations were significantly elevated in the breast cancer cohort at all examined time points and decreased after treatment. VEGF-A levels two years after chemotherapy correlated with increased cancer related mortality, no such correlation could be found between VEGF-A165b and the examined clinical characteristics. Compared to controls, VEGF-A/VEGF-A165b ratios were decreased in patients before and after chemotherapy. Our data suggests that circulating VEGF-A165b is significantly reduced in women with primary breast cancer at time of diagnosis; furthermore, levels change during adjuvant treatment.
抗血管生成剪接变体 VEGF-A165b 在多种癌症实体中下调,但目前对于循环血浆水平知之甚少。本分析解决了这个问题,并在接受过原发性乳腺癌手术的女性高危乳腺癌患者群体中检查了循环 VEGF-A/VEGF-A165b 水平。在 SUCCES-A 试验中,在接受辅助化疗前(1)、化疗后 4 周(2)和 2 年(3),共招募了 205 名患者,并使用 ELISA 测定 VEGF-A/VEGF-A165b 浓度,与临床特征相关联,与健康对照组(n=107)进行比较。化疗完成后 VEGF 水平显著升高。在乳腺癌队列中,化疗完成两年后 VEGF-A165b 水平增加。在所有检查时间点,乳腺癌队列中的 VEGF-A 血浆浓度均显著升高,并在治疗后下降。化疗两年后的 VEGF-A 水平与癌症相关死亡率增加相关,而 VEGF-A165b 与检查的临床特征之间无相关性。与对照组相比,化疗前后患者的 VEGF-A/VEGF-A165b 比值降低。我们的数据表明,在原发性乳腺癌诊断时,女性的循环 VEGF-A165b 明显降低;此外,在辅助治疗期间水平会发生变化。