Elevated circulating level of osteopontin is associated with advanced disease state of non-small cell lung cancer

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.