Rodero Mathieu, Marie Yannick, Coudert Mathieu, Blondet Emmeline, Mokhtari Karima, Rousseau Audrey, Raoul William, Carpentier Catherine, Sennlaub Florian, Deterre Philippe, Delattre Jean-Yves, Debré Patrice, Sanson Marc, Combadière Christophe
Laboratoire d'Immunologie Cellulaire, L'Institut National de Santé et de Recherche Médicale U543, Paris, France.
J Clin Oncol. 2008 Dec 20;26(36):5957-64. doi: 10.1200/JCO.2008.17.2833. Epub 2008 Nov 10.
Few reliable prognostic molecular markers have been characterized for glioblastoma multiforme (GBM), considered the deadliest of human cancers. We hypothesized that genetic polymorphisms in chemokines and their receptors, which together control microglial cell mobilization, may influence survival.
Distributions of one polymorphism of the chemokine CCL2 (-2518A<G) and two polymorphisms of the chemokine receptor CX3CR1 (termed V249I and T280M) were determined in a prospective series of 230 patients with GBM and correlated with overall survival. The replication study used data from a retrospective series of 106 additional patients with GBM. The extent of microglial cell infiltration was assessed by immunochemistry in 102 tumor specimens.
Survival analysis showed that the common CX3CR1-I249 allele was an independent favorable prognostic factor in both groups, prospective and retrospective, with hazard ratios of 0.619 (95% CI, 0.451 to 0.850; P = .0031) and 0.354 (95% CI, 0.217 to 0.580; P < .0001), respectively. This beneficial effect was observed only in patients who underwent surgery. Patients with only this CX3CR1-I249 allele had a substantially longer mean survival (23.5 v 14.1 months; P < .0001). The CCL2-2518G allele was not associated with patient survival. Immunohistochemical analysis of primary tumor biopsies showed that the common CX3CR1 variant allele was associated with reduced microglial cell infiltration.
The common CX3CR1 allelic variant was associated with increased GBM survival and with reduced tumor infiltration by microglia. The CX3CR1 polymorphism does not seem to be a risk factor for GBM but may prove useful in predicting survival.
多形性胶质母细胞瘤（GBM）是人类最致命的癌症之一，目前几乎没有可靠的预后分子标志物。我们推测，共同控制小胶质细胞动员的趋化因子及其受体的基因多态性可能会影响生存率。
在230例GBM患者的前瞻性队列中，测定趋化因子CCL2的一种多态性（-2518A<G）和趋化因子受体CX3CR1的两种多态性（称为V249I和T280M）的分布，并将其与总生存率相关联。复制研究使用了另外106例GBM患者的回顾性队列数据。通过免疫化学方法对102份肿瘤标本中的小胶质细胞浸润程度进行评估。
生存分析表明，常见的CX3CR1 - I249等位基因在前瞻性和回顾性两组中均为独立的有利预后因素，风险比分别为0.619（95%CI，0.451至0.850；P = 0.0031）和0.354（95%CI，0.217至0.580；P < 0.0001）。仅在接受手术的患者中观察到这种有益效果。仅携带这种CX3CR1 - I249等位基因的患者平均生存期显著更长（23.5对14.1个月；P < 0.0001）。CCL2 - 2518G等位基因与患者生存率无关。原发性肿瘤活检的免疫组织化学分析表明，常见的CX3CR1变异等位基因与小胶质细胞浸润减少有关。
常见的CX3CR1等位基因变异与GBM生存率增加以及小胶质细胞对肿瘤的浸润减少有关。CX3CR1多态性似乎不是GBM的危险因素，但可能在预测生存率方面有用。
