Table 4 The Selleck BVD-523 genotype distribution of nt −443 in the OPN promoter by lung cancer TNM stage   The TNM stages of lung cancer Genotypes I + II III + IV P I + II + III

IV P −443             TT 99 65 1.000 125 39 1.000 CT 72 93 Staurosporine 0.003 123 42 0.798 CC 6 25 <0.001 11 20 <0.001 Effect of SNPs on bone metastasis As shown in Table 2, there were total 31 patients who had CC genotype at nt −443, among them, 20 cases were at stage IV. Surprisingly, all of these 20 cases were diagnosed with bone metastasis. By compared with TT genotype, it demonstrated that CC genotype at nt-443 might significantly increase the risk of development of bone metastasis (p < 0.01). Associations between genotypes in the OPN promoter region and survival Kaplan-Meier estimates of different genotypes at nt −443 in the OPN promoter were shown in Figure 1. The survival rates for patients with the C/C genotype were significantly lower than the survival rates for patients with the other two genotypes (C/T, T/T), and C/T genotype was also significantly lower than the survival rates for patients with

T/T genotype. There were no significant associations between survival and genotypes at the other sites (nt −156 and nt −66, data not shown). Figure 1 Kaplan-Meier survival is significantly lower in lung cancer patients with the C/C genotype as compared to the other two genotypes at nt −443 in TGF-beta inhibitor OPN promoter. Discussion Based on my knowledge, it is first time to report the relationship between OPN polymorphisms and cAMP bone metastasis among NSCLC patients. Lots of evidence suggests that OPN plays a role in the regulation of tumor metastasis

and that OPN expression is particularly high in metastatic tumors [20–22]. OPN is overexpressed in cancers that have a high propensity for forming bone metastases. In bone metastases, OPN is generally associated with the interface between the carcinoma and the bone surface, and this appears to be related to increased bone resorptive activity by osteoclasts [23]. Moreover, high OPN expression in the primary tumor is associated with early metastasis and poor clinical outcome in human gastric cancer and other cancers [19, 20, 24–27]. A recent study suggested that the OPN promoter was associated with NSCLC [28]. In the present study, we focused on the association of these SNPs with TNM stages of lung cancer, especially for bone metastasis. Although the distribution of genotypes in the OPN promoter was not significantly different between lung cancer patients and healthy controls, there were significant differences in the distribution of genotypes (CC) at nt −443 between patients with stage IV and other stage lung cancer (Table 4). The survival rates for patients with the C/C genotype were significantly lower than the survival rates of the other two genotypes (C/T, T/T; Figure 1).