Pharmacogenetic profiling of CD133 is associated with response rate (RR) and progression-free survival (PFS) in patients with metastatic colorectal cancer (mCRC), treated with bevacizumab-based chemotherapy.
Pharmacogenetic profiling of CD133 is associated with response rate (RR) and progression-free survival (PFS) in patients with metastatic colorectal cancer (mCRC), treated with bevacizumab-based chemotherapy.
复制标题
CD133的药物遗传学分析与转移性结直肠癌（MCRC）患者的反应率（RR）和无进展生存率（PFS）有关，该患者接受了基于贝伐单抗的化学疗法治疗。
DOI：
10.1038/tpj.2011.61
复制
发表时间：
2013-04
期刊：
影响因子：
--
通讯作者：
Lenz HJ
中科院分区：
文献类型：
--
作者：
Pohl A;El-Khoueiry A;Yang D;Zhang W;Lurje G;Ning Y;Winder T;Hu-Lieskoven S;Iqbal S;Danenberg KD;Kahn M;Teo JL;Shriki J;Stebbing J;Lenz HJ
最近的研究表明，CD133（一种广泛用于分离结肠癌干细胞的表面蛋白）与肿瘤血管生成和复发有关。我们假设 CD133 的基因表达水平和种系变异将预测接受 5-FU、奥沙利铂和贝伐单抗一线治疗的 mCRC 患者的临床结果，并且我们研究了 CD133、血管内皮生长因子 (VEGF) 及其受体的基因表达水平是否存在相关性。我们通过定量 RT-PCR 评估了 54 名患者的肿瘤内基因表达水平，并通过 PCR-RFLP 评估了 91 名患者的基因组 DNA 的 CD133 基因的 3 个种系变异。 CD133 的高基因表达水平 (>7.76) 比低表达水平的患者 (≤7.76，RR=38%，调整后的 p=0.003) 赋予显着更高的肿瘤反应 (RR=86%)，与 VEGF 或其受体基因表达水平无关。 CD133 的基因表达水平与 VEGF 及其受体 mRNA 水平显着相关（VEGFR-1 (p<.01)、-2 和 -3，p<0.05）。两种多态性的联合分析显示，在多变量分析中，两种多态性与 PFS 显着相关（18.5 个月 vs 9.8 个月，p=0.004），作为 PFS 的独立预后因素（调整后的 p=0.002）。这些结果表明 CD133 是转移性结直肠癌中基于贝伐单抗的标准一线治疗的预测标志物。
Recent studies suggest CD133, a surface protein widely used for isolation of colon cancer stem cells, to be associated with tumor angiogenesis and recurrence. We hypothesized that gene expression levels and germline variations in CD133 will predict clinical outcome in patients with mCRC, treated in first-line setting with 5-FU, oxaliplatin and bevacizumab and we investigated whether there is a correlation with gene expression levels of CD133, vascular endothelial growth factor (VEGF) and its receptors. We evaluated intra-tumoral gene expression levels by quantitative RT-PCR from 54 patients and 3 germline variants of the CD133 gene by PCR-RFLP from 91 patients with genomic DNA. High gene expression levels of CD133 (>7.76) conferred a significantly greater tumor response (RR=86%) than patients with low expression levels (≤7.76, RR=38%, adjusted p=0.003), independent of VEGF or its receptor gene expression levels. Gene expression levels of CD133 were significantly associated with VEGF and its receptors mRNA levels (VEGFR-1 (p<.01), -2, and -3, p<0.05). Combined analyses of two polymorphisms showed a significant association with PFS (18.5 months vs 9.8 months, p=0.004), in multivariate analysis as an independent prognostic factor for PFS (adjusted p=0.002). These results suggest CD133 is a predictive marker for standard first-line bevacizumab-based treatment in mCRC.
登录
查看更多内容
影响因子：
20.1
作者：
Barcelos LS;Duplaa C;Kränkel N;Graiani G;Invernici G;Katare R;Siragusa M;Meloni M;Campesi I;Monica M;Simm A;Campagnolo P;Mangialardi G;Stevanato L;Alessandri G;Emanueli C;Madeddu P
通讯作者：
Madeddu P
影响因子：
2
作者：
BERRY, G;KITCHIN, RM;MOCK, PA
通讯作者：
MOCK, PA
影响因子：
64.8
作者：
O'Brien, Catherine A.;Pollett, Aaron;Dick, John E.
通讯作者：
Dick, John E.
影响因子：
11.2
作者：
Collins, AT;Berry, PA;Maitland, NJ
通讯作者：
Maitland, NJ
影响因子：
82.9
作者：
Willett, CG;Boucher, Y;Jain, RK
通讯作者：
Jain, RK