Background: In search of novel biomarkers of response to bevacizumab in metastatic colorectal cancer (mCRC), we analyzed the expression and prognostic role of several proteins related to angiogenesis. Methods: A retrospective, multicenter study on 80 surgical samples from mCRC patients treated in first line with bevacizumab plus chemotherapy was accomplished. The following proteins were analyzed by immunohistochemistry: hERG1 potassium channel, β1-integrin, pAKT, NFkB, HIF-1α, HIF-2α, p53, VEGF-A, GLUT-1, and CA-IX. Data were analyzed in conjunction with the clinicopathological characteristics of the patients, KRAS status, response to bevacizumab, and follow-up. Results: (1) All the proteins were expressed in the samples, with statistically significant associations between HIF-1α and gender, HIF-2α and left colon, hERG1 and VEGF-A, β1-integrin and HIF-2α, GLUT-1 and both HIF-1α and HIF-2α, and CA-IX and VEGF-A. (2) At the univariate analysis, positivity for hERG1, VEGF-A, and the active form of HIF-2α (aHIF-2α), and the G3 histological grade showed a positive impact on progression-free survival (PFS). (3) hERG1 and aHIF-2α maintained their positive impact on PFS at the multivariate analysis. (4) hERG1 behaved as a protective factor for PFS independently on KRAS status. Conclusions: hERG1 and aHIF-2α might help to identify patients who would benefit from bevacizumab treatment.

背景：为了寻找贝伐单抗在转移性结直肠癌（mCRC）中反应的新型生物标志物，我们分析了几种与血管生成相关的蛋白的表达和预后作用。方法：对一线接受贝伐单抗联合化疗的mCRC患者的80例手术样本进行了一项回顾性多中心研究。通过免疫组织化学分析了以下蛋白质：hERG1钾通道，β1-整合素，pAKT，NFkB，HIF-1α，HIF-2α，p53，VEGF-A，GLUT-1和CA-IX。结合患者的临床病理特征，KRAS状态，对贝伐单抗的反应和随访情况对数据进行分析。结果：（1）所有蛋白均在样品中表达，HIF-1α与性别，HIF-2α与左结肠，hERG1和VEGF-A，β1-整合素和HIF-2α，GLUT-1和HIF均具有统计学意义-1α和HIF-2α，以及CA-IX和VEGF-A。（2）在单变量分析中，hERG1，VEGF-A和HIF-2α的活性形式（aHIF-2α）的阳性以及G3的组织学等级对无进展生存期（PFS）有积极影响。（3）在多变量分析中，hERG1和aHIF-2α对PFS保持积极影响。（4）hERG1是独立于KRAS状态的PFS保护因子。结论： hERG1和aHIF-2α可能有助于确定将受益于贝伐单抗治疗的患者。