Osteopontin genetic variants are associated with overall survival in advanced non-small-cell lung cancer patients and bone metastasis

PURPOSE: Osteopontin (OPN) plays important roles in the modulation of apoptosis, angiogenesis, immune response, and tumor invasion. Elevated osteopontin expression has been reported in the lung cancer tissues compared to counterpart normal tissues. This study examined whether genetic variations in the osteopontin gene are associated with survival of lung cancer patients and occurrence rate of bone metastasis. EXPERIMENTAL DESIGN: Three hundred and sixty patients with stages I to IV between 2003 and 2007 were recruited in this study and same number of healthy persons were used as control. Three promoter osteopontin polymorphisms, OPN-66 T/G, -156G/GG, and -443C/T variants were genotyped using DNA from blood lymphocytes. Chi-square test and a Fisher’s exact test were used to analyze the genotype distribution among TNM stages and incidence of bone metastasis and lymph mode metastasis. Kaplan-Meier method and log-rank test were used to compare survival by different genotypes. RESULTS: For the variant at nt −443 (CC), there was a significant difference between the number of patients with stage IV and those with all other stages of lung cancer (p < 0.01). Patients with −443 (CC) variant had significant higher incidence of bone metastasis development compared to other genotypes. For the variant at nt −443 (CT), there was a significant difference between the number of lung cancer patients with stage III + IV and those with stage I + II (P < 0.01). The survival rates for patients with the C/C genotype were significantly lower than for patients with the other two genotypes (C/T, T/T). CONCLUSION: OSTEOPONTIN −443C/T polymorphism is a potential predictive marker of survival in lung cancer patients, it is correlated with bone metastasis significantly.