CCL25、AKT、VEGF-D和MMP-9蛋白在非小细胞肺癌患者术前血清中的水平及其临床意义

Preoperative serum CCL25,AKT,VEGF-D and MMP-9 protein levels in patients with non-small cell lung cancer and its clinical significance

目的:探讨CCL25、AKT、VEGF-D和MMP-9蛋白在非小细胞肺癌(NSCLC)患者术前血清中的水平及其与患者临床病理特征的关系。方法:选取2014年9月至2015年4月在广西壮族自治区人民医院接受治疗的60例NSCLC患者作为观察组,另选取同期于本院行正常体检的60例健康志愿者作为对照组,采用酶联免疫吸附试验(ELISA)法检测血清CCL25、AKT、VEGF-D和MMP-9的水平,分析CCL25、AKT、VEGF-D和MMP-9蛋白与NSCLC患者临床病理特征的关系。结果:NSCLC患者术前血清中CCL25、AKT、VEGF-D和MMP-9蛋白的水平均显著高于对照组(均P<0.001)。CCL25、AKT、VEGF-D和MMP-9蛋白水平与NSCLC患者原发肿瘤大小、淋巴结转移、病理类型和TNM分期等存在相关性(均P<0.05),与患者性别、年龄无明显相关关系(P>0.05)。ROC曲线分析结果显示,以血清CCL25水平334ng/L为临界值,诊断淋巴结转移的敏感度为74.2%,特异度为86.2%;以AKT蛋白水平345ng/L为临界值,其敏感度为71.0%,特异度为96.6%;以VEGF-D蛋白水平362ng/L为临界值,其敏感度为90.3%,特异度为96.6%;以MMP-9蛋白水平374μg/L为临界值,其敏感度为71.0%,特异度为89.7%。NSCLC患者术前血清CCL25蛋白水平与AKT、VEGF-D、MMP-9蛋白水平均呈正相关关系(r=0.863、0.785、0.881,均P<0.001)。结论:NSCLC患者术前血清CCL25、AKT、VEGF-D和MMP-9蛋白水平升高,且与肺癌的发生、发展和淋巴结转移有密切联系;AKT通路及其效应细胞因子VEGF-D和MMP-9有可能受CCR9/CCL25生物轴调节。

Objective： To investigate the preoperative serum levels of CCL25, AKT, VEGF-D and MMP-9 in non-small cell lung cancer （NSCLC） patients, and their correlation with clinical pathologic characteristics. Methods： 60 NSCLC patients and 60 healthy controls who were treated in our hospital from September 2014 to April 2015 were selected. The serum CCL25, AKT, VEGF-D and MMP-9 protein levels were measured by enzyme linked immunosorbent assay （ELISA）. The association of preoperative serum CCL25, AKT, VEGF-D and MMP-9 protein levels in NSCLC patients and their clinical pathologic characteristics were studied. Results： The serum CCL25, AKT, VEGF-D and MMP-9 protein levels of NSCLC patients were significantly higher than those of controls （ P 〈0. 001）. The CCL25, AKT, VEGF-D and MMP-9 protein levels were significantly correlated with tumor size, lymph node involvement, pathological pattern and TNM stage （ P 〈0.05）, but not with the age and sex （ P〉0.05）. ROC analysis showed that serum CCL25 was 74. 2% in sensitivity and 86.2% in specificity with a cut-off value of 334 ng/L for diagnosis of lymphatic metastasis, while AKT was 71.0% in sensitivity and 96. 6% in specificity with a cut-off value of 345 ng/L, VEGF-D was 90.3% in sensitivity and 96.6% in specificity with a cut-off value of 362 ng/L, and MMP-9 was 71.0% in sensitivity and 89.7% in specificity with a cut-off value of 374 ng/L. The preoperative serum CCL25 level was positively associated with AKT, VEGF-D and MMP-9 protein levels （ r = 0. 863, 0. 785 and 0. 881, respectively; P〈0. 001）. Conclusion： Increased serum CCL25, AKT,VEGF-D and MMP-9 protein levels before operation were correlated with the development and lymphatic metastasis of lung cancer. AKT pathway and its downstream cytokines VEGF-D and MMP- 9 may be regulated by CCL25/CCR9 biological axis in this process.