Prognostic value of circulating VEGFR2⁺ bone marrow-derived progenitor cells in patients with advanced cancer

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• 作者：Christophe Massard^a ; ^c ; Isabelle Borget^b ; Marie Cé ; cile Le Deley^b ; Melissa Taylor^c ; ^d ; Carlos Gomez-Roca^a ; Jean Charles Soria^a ; ^c ; Franç ; oise Farace^c ; ^d ; ^{farace@igr.fr}
• 关键词：Circulating bone marrow derived progenitor cells ; Circulating endothelial cells ; Angiogenesis biomarker ; Prognosis ; Advanced cancers
• 刊名：European Journal of Cancer
• 出版年：2012
• 期刊代码：88_09598049
• 类别：med
• 出版时间：June, 2012
• 卷：48
• 期：9
• 页码：1354-1362
• 文件大小：803 K

摘要

We hypothesised that host-related markers, possibly reflecting tumour aggressiveness, such as circulating endothelial cells (CEC) and circulating VEGFR2⁺ bone marrow-derived (BMD) progenitor cells, could have prognostic value in patients with advanced cancer enrolled in early anticancer drug development trials.

Baseline CECs (CD45^-CD31⁺CD146⁺7AAD^- cells) and circulating VEGFR2⁺-BMD progenitor cells (defined as CD45^dimCD34⁺VEGFR2⁺7AAD^- cells) were measured by flow-cytometry in 71 and 58 patients included in phase 1 trials testing novel anti-vascular or anti-angiogenic agents. Correlations between levels of CECs, circulating VEGFR2⁺-BMD progenitor cells, clinical and biological prognostic factors (i.e. the Royal Marsden Hospital (RMH) score), and overall survival (OS) were studied.

The median value of CECs was 12 CEC/ml (range 0-154/ml). The median level of VEGFR2⁺-BMD progenitor cells was 1.3%(range 0-32.5%) of circulating BMD-CD34⁺ progenitors. While OS was not correlated with CEC levels, it was significantly worse in patients with high VEGFR2⁺-BMD progenitor levels (>1%) (median OS 9.0 versus 17.0 months), and with a RMH prognostic score >0 (median OS 9.0 versus 24.2 months). The prognostic value of VEGFR2⁺-BMD progenitor levels remained significant (hazard ratio (HR) = 2.3, 95%confidence interval (CI), 1.1-4.6, p = 0.02) after multivariate analysis. A composite VEGFR2⁺-BMD progenitor level/RHM score 猢? was significantly associated with an increased risk of death compared to scores of 0 or 1 (median OS 9.0 versus 18.4 months, HR = 2.6 (95% CI, 1.2-5.8, p = 0.02)).

High circulating VEGFR2⁺-BMD progenitor levels are associated with poor prognostics and when combined to classical clinical and biological parameters could provide a new tool for patient selection in early anticancer drug trials.