Abstract：
Bevacizumab-induced hypertension poses a therapeutic challenge and identifying biomarkers for hypertension can enhance therapy safety. Lower plasma levels of VEGF-A, angiopoietin-2, and rs6770663 in KCNAB1 were previously associated with increased risk of bevacizumab-induced hypertension. This study investigated whether these factors independently contribute to grade 2-3 bevacizumab-induced hypertension risk in 277 cancer patients (CALGB/Alliance 90401). Multivariable analyses assessed the independent association of each factor and hypertension. Likelihood ratio test (LRT) evaluated the explanatory significance of combining protein levels and rs6770663 in predicting hypertension. Boostrap was employed to assess the mediation effect of protein levels on the rs6770663 association with hypertension. Lower protein levels and rs6770663 were independently associated with increased hypertension risk. Adding rs6770663 to protein levels improved the prediction of hypertension (LRT p = 0.0002), with no mediation effect observed. Protein levels of VEGF-A, angiopoietin-2 and rs6770663 in KCNAB1 are independent risk factors and, when combined, may improve prediction of bevacizumab-induced hypertension. ClinicalTrials.gov Identifier: NCT00110214.
摘要：
贝伐单抗诱导的高血压提出了治疗挑战，识别高血压的生物标志物可以提高治疗安全性。降低血浆VEGF-A水平,KCNAB1中的血管生成素-2和rs6770663以前与贝伐单抗诱导的高血压风险增加相关.这项研究调查了这些因素是否独立地导致277名癌症患者的2-3级贝伐单抗诱导的高血压风险（CALGB/Alliance90401）。多变量分析评估了每个因素与高血压的独立关联。似然比检验（LRT）评估了结合蛋白质水平和rs6770663预测高血压的解释意义。Boostrap用于评估蛋白质水平对rs6770663与高血压相关的调解作用。较低的蛋白质水平和rs6770663与高血压风险增加独立相关。将rs6770663添加到蛋白质水平改善了高血压的预测（LRTp=0.0002），没有观察到调解效果。VEGF-A的蛋白质水平,KCNAB1中血管生成素-2和rs6770663是独立的危险因素,当合并时，可以改善贝伐单抗诱发高血压的预测。ClinicalTrials.gov标识符：NCT00110214。
