Reduction of elevated plasma osteopontin levels with resection of non-small cell lung cancer (NSCLC)

Abstract

11019 Background: Plasma osteopontin (OPN) levels in advanced NSCLC correlate with response to therapy and survival but the role plasma OPN in diagnosis or monitoring of early stage NSCLC has not been investigated. We hypothesize that plasma OPN levels are elevated in early stage NSCLC and that resection results in a measurable reduction. Methods: Pre-operative (pre-op) plasma OPN levels (ng/ml) were measured by ELISA (IBL-Japan) in a discovery set of 60 early stage NSCLC patients and compared to 56 current or former smokers. Pre-op OPN was validated in an independent cohort of 78 resectable NSCLC patients. The pre-op OPN level in the latter cohort was compared to matched postoperative (post-op) OPN levels to monitor the impact of surgery on the biomarker. Results: Discovery set pre-op OPN (271+31) was significantly higher than in smokers (40+2)(p=.001). Pre-op OPN was similar in the validation cohort (357+31, p=.055, demographics in Table ). Post-op OPN (189+19) measured at mean of 23 weeks (range 2–105) was significantly lower than pre-op (p<.0001). Time from surgery significantly impacted post-op OPN, with OPN<6 weeks post-op (282+30) higher than OPN>6 weeks post-op (155+18)(p<.0001). After 6 weeks post-op, resected stage I patients (N=45) had a significant decrease in OPN levels from 373+45 to 142+21 (p<.0001). Multivariate analysis ( Table ) noted a significant correlation between age, albumin and pre-op OPN, and between albumin and pre-op OPN and >6 weeks post-op OPN. No correlation was noted between gender, smoking, histology, diabetes or stage and the pre- or >6 weeks post-op OPN. Conclusions: Plasma OPN levels in early stage NSCLC patients are significantly elevated compared to smokers. The elevated pre-op OPN levels were validated in an independent cohort of early stage NSCLC patients. A significant decrease in OPN was noted following resection. Peri-operative reductions in plasma OPN may serve as a marker for response to therapy and warrant investigation into prognostic significance in early stage NSCLC. [Table: see text] [Table: see text]