Soluble CD40 ligand plasma levels in lung cancer

Soluble CD40 ligand plasma levels in lung cancer
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DOI:
10.1158/1078-0432.ccr-0348-03
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发表时间:
2004-01-15
影响因子:
11.5
通讯作者:
Ferroni, P
Ferroni, P
中科院分区:
医学1区
文献类型:
--
作者:
Roselli, M;Mineo, TC;Ferroni, P

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目的:肿瘤诱导的血小板活化可引起多种细胞因子的释放,包括CD 40配体(CD 40 L)。人肿瘤中CD 40/CD 40 L通路的激活可能导致凝血酶产生,已知凝血酶参与血管生成。因此,我们调查是否可溶性(S)CD 40 L水平增加,肺癌患者作为血小板和/或凝血activation.Experimental设计:柠檬酸血浆样本从120例不同阶段和组织型的肺癌和60个年龄和性别匹配的对照组。sCD 40 L,sP-选择素(血小板活化标志物)、凝血酶原片段1 + 2和凝血酶-抗凝血酶III复合物水平结果:肺癌患者sCD 40 L水平中位数高于对照组(0.46对0.13 ng/ml; P < 0.0001),尽管与疾病分期的相关性不明显。尽管如此,sCD 40 L水平在鳞癌中显著高于腺癌(0.75 vs 0.27 ng/ml; P < 0.05)。此外,IV期肺癌患者sCD 40 L水平中位数高于非转移性鳞癌患者(1.02 vs 0.61 ng/ml; P < 0.05)。sCD 40 L水平与sP-选择素显著相关凝血酶原片段1 + 2(P < 0.001)(P < 0.001),或凝血酶-抗凝血酶III复合物而在肺鳞癌中,sP-选择素(P = 0.011)与sCD 40 L独立相关。这些结果表明,sCD 40 L水平升高,可以优先发现在晚期鳞状细胞癌患者,并提供证据表明,这种细胞因子的水平增加与体内血小板活化的发生。
Purpose: Tumor-induced platelet activation may cause the release of various cytokines, including CD40 ligand (CD40L). Activation of the CD40/CD40L pathway in human tumors may result in thrombin generation, which is known to be involved in angiogenesis. Thus, we investigated whether soluble (s)CD40L levels are increased in patients with lung cancer as a result of platelet and/or coagulation activation.Experimental Design: Citrated plasma samples were obtained from 120 patients with different stages and histotypes of lung cancer and 60 age- and sex-matched control subjects. sCD40L, sP-selectin (marker of platelet activation), prothrombin fragment 1 + 2, and thrombin-antithrombin III complex levels (both markers of coagulative activation) were measured in all samples.Results: Patients with lung cancer had median sCD40L levels higher than in control subjects (0.46 versus 0.13 ng/ml; P < 0.0001), although correlation with the stage of disease was not evident. Nonetheless, sCD40L levels were significantly higher in squamous cancer compared with adenocarcinoma (0.75 versus 0.27 ng/ml; P < 0.05). Moreover, median sCD40L levels were higher in stage IV compared with nonmetastatic squamous lung cancer (1.02 versus 0.61 ng/ml; P < 0.05). sCD40L levels significantly correlated with sP-selectin (P < 0.001), prothrombin fragment 1 + 2 (P < 0.001), or thrombin-antithrombin III complex (P < 0.05) in squamous lung cancer, but only sP-selectin (P = 0.011) was independently related to sCD40L.Conclusions: These findings indicate that elevated sCD40L levels can be preferentially found in patients with advanced squamous cancer and provide evidence that increased levels of this cytokine are associated to the occurrence of in vivo platelet activation.