Background: Colorectal cancer is among the most prevalent causes of tumor-related deaths worldwide. Antiangiogenic therapy represents a cornerstone of metastatic CRC treatment, and biomarkers are advocated for the optimization of this therapeutic strategy. Methods: In this observational prospective study, we employed an optimized flow cytometry protocol to investigate the prognostic and predictive potential of blood circulating endothelial cells (CECs), circulating endothelial progenitor cells (CEPCs), and related subsets in a cohort of patients with metastatic colorectal cancer (n= 40). Results: Computational FC analysis revealed a differential enrichment of blood cell clusters with a CD34+/CD45dim/CD117(c-kit)+ phenotype between responders and non-responders both to antiangiogenic and non-antiangiogenic treatments. Intriguingly, our results show that a high percentage of annexin V-negative cells in a putative circulating progenitor population with a CD34+/CD45dim/CD117+ phenotype was correlated with a reduced response to systemic anticancer treatments (p= 0.015) and worse overall survival (log-rankp= 0.03). In addition, we observed increased blood concentrations of CD34+/CD45dim/CD117+/annexin V- cells in patients with a higher number of metastatic sites (p= 0.03). Conclusions: Overall, these findings hold promise for the identification of novel circulating biomarkers to develop more personalized treatment approaches in patients with metastatic colorectal cancer.
背景：结直肠癌是全球范围内导致肿瘤相关死亡的主要原因之一。抗血管生成治疗是转移性结直肠癌治疗的基石，而生物标志物的应用有助于优化这一治疗策略。方法：在这项观察性前瞻性研究中，我们采用优化的流式细胞术方案，探讨了循环内皮细胞、循环内皮祖细胞及其相关亚群在一组转移性结直肠癌患者（n=40）中的预后和预测价值。结果：流式细胞术计算分析显示，在抗血管生成治疗与非抗血管生成治疗的反应者和无反应者之间，具有CD34+/CD45dim/CD117(c-kit)+表型的血细胞簇存在差异富集。值得注意的是，我们的研究结果表明，在具有CD34+/CD45dim/CD117+表型的假定循环祖细胞群中，膜联蛋白V阴性细胞的高比例与对全身抗癌治疗的反应降低（p=0.015）以及较差的总生存期（对数秩检验p=0.03）相关。此外，我们观察到转移灶数量较多的患者中，CD34+/CD45dim/CD117+/膜联蛋白V-细胞的血液浓度升高（p=0.03）。结论：总体而言，这些发现为识别新型循环生物标志物提供了希望，有助于为转移性结直肠癌患者制定更个性化的治疗方案。
肿瘤(癌症)患者之家