Levels of circulating CD45(dim)CD34(+)VEGFR2(+) progenitor cells correlate with outcome in metastatic renal cell carcinoma patients treated with tyrosine kinase inhibitors.
Levels of circulating CD45(dim)CD34(+)VEGFR2(+) progenitor cells correlate with outcome in metastatic renal cell carcinoma patients treated with tyrosine kinase inhibitors.
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DOI：
10.1038/bjc.2011.72
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发表时间：
2011-03-29
影响因子：
8.8
通讯作者：
Escudier, B.
中科院分区：
文献类型：
--
作者：
Farace, F.;Gross-Goupil, M.;Tournay, E.;Taylor, M.;Vimond, N.;Jacques, N.;Billiot, F.;Mauguen, A.;Hill, C.;Escudier, B.
关键词：
预测抗血管生成治疗的疗效对转移性肾细胞癌（mRCC）患者具有临床价值。我们验证了循环内皮细胞（CEC）、骨髓来源的CD45dimCD34+VEGFR2+祖细胞或血浆血管生成因子水平与接受酪氨酸激酶抑制剂（TKI）治疗的mRCC患者的临床结果相关的假设。在治疗期间，55名mRCC患者在基线（第1天）和第14天进行前瞻性监测（46名患者接受舒尼替尼治疗，9名患者接受索拉非尼治疗）。采用四色流式细胞术（FCM）在1ml全血中检测循环内皮细胞（CD45−CD31+CD146+7-氨基放线菌素(7AAD)−细胞）。循环CD45dimCD34+VEGFR2+7AAD−祖细胞通过四色流式细胞仪检测富集祖细胞。ELISA法检测血浆VEGF、sVEGFR2、SDF-1α、sVCAM-1水平。研究了基线CEC、CD45dimCD34+VEGFR2+7AAD -祖细胞、血浆因子以及CEC、CD45dimCD34+VEGFR2+7AAD -祖细胞、血浆因子水平、TKI应答、无进展生存期（PFS）和总生存期（OS）之间的相关性。标记物与TKI疗效之间无显著相关性。基线CEC、血浆VEGF、sVEGFR-2、SDF-1α、sVCAM-1水平与PFS和OS无相关性。然而，基线CD45dimCD34+VEGFR2+7AAD−祖细胞水平与PFS （P=0.01）和OS （P=0.006）相关。该人群和SDF-1α水平在第1天和第14天之间的变化与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CD45dimCD34+VEGFR2+祖细胞、血浆VEGF和SDF-1α水平可能对tki治疗的mRCC患者的预后有临床意义。
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 CD45dimCD34+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 CD45dimCD34+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, CD45dimCD34+VEGFR2+7AAD− progenitor cells, plasma factors, as well as day 1–day 14 changes in CEC, CD45dimCD34+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 CD45dimCD34+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 CD45dimCD34+VEGFR2+ progenitor cells, plasma VEGF and SDF-1α levels could be of clinical interest in TKI-treated mRCC pts to predict outcome.
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影响因子：
8.8
作者：
通讯作者：
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影响因子：
6.6
作者：
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DOI：
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发表时间：
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影响因子：
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