Elevated circulating level of osteopontin is associated with advanced disease state of non-small cell lung cancer
Elevated circulating level of osteopontin is associated with advanced disease state of non-small cell lung cancer
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DOI：
10.1016/j.lungcan.2007.04.005
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发表时间：
2007-09-01
期刊：
影响因子：
5.3
通讯作者：
Kim, Se Kyu
中科院分区：
文献类型：
--
作者：
Chang, Yoon Soo;Kim, Hyung Jung;Kim, Se Kyu
骨桥蛋白(OPN)通过与Cpn受体如α(V)、β(β)整合素和CD44结合，在肿瘤的进展和转移中发挥重要作用，其在肿瘤中的过度表达与NSCLC患者的临床预后不良有关。采用双抗体夹心酶联免疫吸附试验检测130例非小细胞肺癌患者外周血中OPN水平，根据临床、病理参数和OPN基因启动子单核苷酸多态性(SNPs)进行分析。进展期OPN水平较高(T4与T1-3、N3与NO-2、M1与MO，分别P=0.029、.001、.001，Kruskat-Wattis H检验)，反映出较高水平。OPN在IV期高于I-III期(P=.029，Kruskat-Wattis H检验)。在临床上。病理参数包括年龄、性别、吸烟状况、组织学亚型和分化程度、吸烟状况影响循环OPN水平，表明戒烟者Cpn水平高于现吸烟者和不吸烟者(P=0.038，Kruskal-WathsH检验)。OPN基因启动子-443位核苷酸变异对循环Cpn水平无影响，但-156位G/G携带者的OPN浓度高于G/GG或GG/GG携带者(P=0.003，Kruskal-Wallis H检验)。与早期(I-IIIA)非小细胞肺癌(I-IIIA)相比，NT-156位G/G的患者更容易被诊断为晚期(IIIB-IV)(P=0.048，Mantel-Haenszel检验)。在多因素分析中，分期是影响OPN循环水平的唯一独立因素。尽管有骨转移组的OPN水平高于无骨转移组(P=0.028，Mann-Whitney U检验)，但骨转移组与非骨转移组之间的OPN水平无明显差异。鉴于OPN水平的升高与晚期NSCLC相关，阐明OPN的调节机制可能有助于开发一种新的NSCLC治疗方法。(C)2007年爱思唯尔爱尔兰有限公司版权保留。
Osteopontin (OPN) plays important rotes in tumor progression and metastasis through binding to CPN receptors such as alpha(V)beta(beta) integrin and CD44, and its overexpression in tumor is associated poor clinical outcome of NSCLC patients. Circulating OPN levels, measured by ELISA in 130 NSCLC cases that had not been treated for cancer at the time of sampling, were analyzed according to clinical, pathologic parameters and single nucleotide polymorphisms (SNPs) in the OPN gene promoter. Advanced disease states had higher circulating levels of OPN (T4 versus T1-3, N3 versus NO-2, and M1 versus MO, P=.029, .001, and .001, respectively, Kruskat-Wattis H-test), reflected by higher level. of OPN in stage IV than stage I-III (P=.029, Kruskat-Wattis H-test). Among the clinical. and pathological parameters including age, gender, smoking status, histologic subtypes and grade of differentiation, smoking status influences circulating OPN level showing higher level of CPN in ex-smokers than current and non-smokers (P=.038, Kruskal-Waths H-test). Variation at nucleotide (nt) -443 of the OPN gene promoter had no influence on circulating CPN levels, however, patients with G/G at nt -156 showed higher concentrations of OPN than those with G/GG or GG/GG (P=.003, Kruskal-Wallis H-test). A patient with G/G at nt -156 was more frequently diagnosed with advanced stage (IIIB-IV) than with early stage (I-IIIA) NSCLC (P=.048, Mantel-Haenszel-test). In multivariate analysis, stage is the only independent factor influencing circulating level of OPN. Although circulating level of OPN in the patients with bone metastasis was higher than in those without bone metastasis (P=.028, Mann-Whitney U-test), there was no difference in the OPN levels between bone metastasis group and non-bone metastasis group. Given that the elevated levels of OPN is associated with advanced stages of NSCLC, elucidating OPN regulatory mechanisms may con tribute to the development of a new therapeutic modality for NSCLC. (c) 2007 Elsevier Ireland Ltd. All. rights reserved.