Translational Research Laboratory, Institut de Cancérologie Gustave Roussy, 114 rue Edouard Vaillant, 94805 Villejuif, France.
Br J Cancer. 2011 Mar 29;104(7):1144-50. doi: 10.1038/bjc.2011.72. Epub 2011 Mar 8.
Predicting the efficacy of antiangiogenic therapy would be of clinical value in patients (pts) with metastatic renal cell carcinoma (mRCC). We tested the hypothesis that circulating endothelial cell (CEC), bone marrow-derived CD45(dim)CD34(+)VEGFR2(+) progenitor cell or plasma angiogenic factor levels are associated with clinical outcome in mRCC pts undergoing treatment with tyrosine kinase inhibitors (TKI).
Fifty-five mRCC pts were prospectively monitored at baseline (day 1) and day 14 during treatment (46 pts received sunitinib and 9 pts received sorafenib). Circulating endothelial cells (CD45(-)CD31(+)CD146(+)7-amino-actinomycin (7AAD)(-) cells) were measured in 1 ml whole blood using four-color flow cytometry (FCM). Circulating CD45(dim)CD34(+)VEGFR2(+)7AAD(-) progenitor cells were measured in progenitor-enriched fractions by four-color FCM. Plasma VEGF, sVEGFR2, SDF-1α and sVCAM-1 levels were determined by ELISA. Correlations between baseline CEC, CD45(dim)CD34(+)VEGFR2(+)7AAD(-) progenitor cells, plasma factors, as well as day 1-day 14 changes in CEC, CD45(dim)CD34(+)VEGFR2(+)7AAD(-) progenitor, plasma factor levels, and response to TKI, progression-free survival (PFS) and overall survival (OS) were examined.
No significant correlation between markers and response to TKI was observed. No association between baseline CEC, plasma VEGF, sVEGFR-2, SDF-1α, sVCAM-1 levels with PFS and OS was observed. However, baseline CD45(dim)CD34(+)VEGFR2(+)7AAD(-) progenitor cell levels were associated with PFS (P=0.01) and OS (P=0.006). Changes in this population and in SDF-1α levels between day 1 and day 14 were associated with PFS (P=0.03, P=0.002). Changes in VEGF and SDF-1α levels were associated with OS (P=0.02, P=0.007).
Monitoring CD45(dim)CD34(+)VEGFR2(+) progenitor cells, plasma VEGF and SDF-1α levels could be of clinical interest in TKI-treated mRCC pts to predict outcome.
在转移性肾细胞癌（mRCC）患者中，预测抗血管生成治疗的疗效具有临床价值。我们检测了这样一种假设，即在接受酪氨酸激酶抑制剂（TKI）治疗的 mRCC 患者中，循环内皮细胞（CEC）、骨髓来源的 CD45（dim）CD34（+）VEGFR2（+）祖细胞或血浆血管生成因子水平与临床结局相关。
55 例 mRCC 患者在基线（第 1 天）和治疗期间（第 14 天）进行前瞻性监测（46 例接受舒尼替尼治疗，9 例接受索拉非尼治疗）。使用四色流式细胞术（FCM）在 1ml 全血中测量循环内皮细胞（CD45（-）CD31（+）CD146（+）7-氨基放线菌素 D（7AAD）（-）细胞）。通过四色 FCM 在祖细胞富集部分测量循环 CD45（dim）CD34（+）VEGFR2（+）7AAD（-）祖细胞。通过 ELISA 测定血浆 VEGF、sVEGFR2、SDF-1α 和 sVCAM-1 水平。检查基线 CEC、CD45（dim）CD34（+）VEGFR2（+）7AAD（-）祖细胞、血浆因子与 TKI 反应、无进展生存期（PFS）和总生存期（OS）之间的相关性。
未观察到标志物与 TKI 反应之间存在显著相关性。基线 CEC、血浆 VEGF、sVEGFR-2、SDF-1α、sVCAM-1 水平与 PFS 和 OS 之间无相关性。然而，基线 CD45（dim）CD34（+）VEGFR2（+）7AAD（-）祖细胞水平与 PFS（P=0.01）和 OS（P=0.006）相关。第 1 天和第 14 天之间该群体和 SDF-1α 水平的变化与 PFS 相关（P=0.03，P=0.002）。VEGF 和 SDF-1α 水平的变化与 OS 相关（P=0.02，P=0.007）。
监测 TKI 治疗的 mRCC 患者中 CD45（dim）CD34（+）VEGFR2（+）祖细胞、血浆 VEGF 和 SDF-1α 水平可能具有预测结局的临床意义。
