Increased pre-surgical numbers of endothelial progenitor cells and circulating endothelial cells in colorectal cancer fail to predict outcome
Increased pre-surgical numbers of endothelial progenitor cells and circulating endothelial cells in colorectal cancer fail to predict outcome
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DOI：
10.1007/s00384-014-2116-3
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发表时间：
2015-01
影响因子：
2.8
通讯作者：
K. Ramcharan;G. Lip;P. Stonelake;A. Blann
中科院分区：
文献类型：
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作者：
K. Ramcharan;G. Lip;P. Stonelake;A. Blann
血管内皮和血管生成是肿瘤治疗的靶点。对治疗的反应可以通过实验室血浆标志物如循环内皮细胞（CEC）、内皮祖细胞（EPC）、血管性血友病因子（vWf）、可溶性E选择素、血管内皮生长因子（VEGF）和血管生成素来评估。我们假设，这些标志物，手术前获得的，将预测2年的结果，手术后有或无抗血管生成治疗结直肠癌（CRC）。MethodsWe招募了154例CRC患者，其中51例单独手术治疗，74例标准化疗（5-氟尿嘧啶）和29例标准化疗加抗VEGF治疗（阿瓦斯丁）。术前采集外周血。CD 34 +/CD 45 −/CD 146 + CEC和CD 34 +/CD 45 −/CD 309 [KDR]+EPCs通过流式细胞术和血浆标志物ELISA.ResultsAfter a mean of 2.1 years follow up（range 1.9-2.3 years），52例患者（33.7%）经历了不良结局（肿瘤扩散或复发的放射学和/或组织学证据，或死亡[n= 26]）。在单变量分析中，不良结局与Dukes分期（p< 0.001）、美国癌症联合委员会（AJCC）分期（p< 0.001）、治疗类型（单纯手术、标准化疗加或不加抗抗原治疗）（p= 0.047）、CEC（p< 0.02）和EPC（p< 0.01）相关。在随后的二元logistic回归分析中，只有Dukes分期（风险比2.3，95%置信区间1.0- 5.3，p = 0.047）和改良AJCC分期（4.62，1.88- 11.33，p < 0.001）预测预后不良。与Dukes或AJCC分期相比，术前测量的CEC、EPCs、vWf、可溶性E选择素和生长因子（VEGF和血管生成素）在预测结直肠癌2年预后方面没有额外的作用。
IntroductionThe endothelium and angiogenesis are therapeutic targets in cancer. Response to treatment may be assessed by laboratory plasma markers such as circulating endothelial cells (CECs), endothelial progenitor cells (EPCs), von Willebrand factor (vWf), soluble E selectin, vascular endothelial growth factor (VEGF) and angiogenin. We hypothesised that these markers, obtained before surgery, would predict 2-year outcome after surgery with or without anti-angiogenic therapy for colorectal cancer (CRC).MethodsWe recruited 154 patients with CRC, of whom 51 were treated with surgery alone, 74 were treated with standard chemotherapy (5-fluorouracil) and 29 were treated with standard chemotherapy plus anti-VEGF therapy (Avastin). Peripheral blood was taken before surgery. CD34+/CD45−/CD146+CECs and CD34+/CD45−/CD309 [KDR]+EPCs were measured by flow cytometry and plasma markers by ELISA.ResultsAfter a mean of 2.1 years follow-up (range 1.9–2.3 years), 52 of the patients (33.7 %) experienced a poor outcome (radiological and/or histological evidence of tumour spread or recurrence, or death [n= 26]). In univariate analysis, poor outcome was linked to Dukes’ stage (p< 0.001), American Joint Committee on Cancer (AJCC) stage (p< 0.001), type of treatment (surgery alone, standard chemotherapy with or without anti-antigenic therapy) (p= 0.047), CECs (p< 0.02) and EPCs (p< 0.01). In subsequent binary logistic regression analysis, only Dukes’ stage (hazard ratio 2.3, 95 % confidence interval 1.0–5.3,p= 0.047) and modified AJCC stage (4.62, 1.88–11.33,p< 0.001) predicted a poor outcome.ConclusionEndothelial cell markers (CECs, EPCs, vWf, soluble E selectin) and growth factors (VEGF and angiogenin), measured before surgery, have nothing extra to offer in predicting 2-year outcome in colorectal cancer when compared to Dukes’ or AJCC stage.