Purpose: The purpose of this study was to better define the role of osteopontin (OPN) and osteonectin [also known as secreted protein acidic and rich in cysteine (SPARC)] in lung tumorigenesis by comparing the expressions of these genes in lung tumor tissue and matched normal tissue and by determining the prognostic significance of the gene expressions.Experimental Design: Quantitative real-time reverse transcription-PCR was used to analyze OPN and SPARC mRNA expression in normal lung tissue and matching tumor samples from 82 patients with non-small cell lung cancer. Gene expression data for each patient were matched to survival data.Results: The overall median mRNA expression level of OPN was about 20-fold higher in tumor tissues than in matching normal lung tissues (P < 0.001), whereas SPARC gene expression was not significantly different in both tissue types. Forty of 82 patients had high (>4.1) intratumoral OPN expression, and 15 of 82 patients had high (>15.5) SPARC expression. High OPN expression in the tumor tissue was associated with inferior survival (P ‫؍‬ 0.014), whereas high SPARC expression showed a trend toward longer survival (P ‫؍‬ 0.095). The impact of high OPN and low SPARC expression on patient survival was additive (P ‫؍‬ 0.001).Conclusions: The large increase in OPN expression in tumors compared with normal tissue and its association with survival suggest a role for OPN in lung tumorigenesis.

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