Abstract
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. 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. 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 (>or=4.1) intratumoral OPN expression, and 15 of 82 patients had high (>or15.5) 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). 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.
Highlights
Lung cancer is one of the most common malignancies in the world and is the leading cause of cancer-related deaths for both men and women in the United States
OPN mRNA expression was detectable by real-time quantitative reverse transcription-PCR (QRT-PCR) in 76 of 82 (92.6%) tumor specimens and 48 of 82 (58.5%) nonmalignant lung specimens
OPN expression was higher in tumor tissue than in the matched normal tissue in 77 of 82 (93.9%) individual cases
Summary
Despite improvements in the detection and treatment of lung cancer in the past two decades, the 5-year survival rate remains Ͻ15% [2]. Osteopontin (OPN), called secreted phosphoprotein 1, and secreted protein acidic and rich in cysteine (SPARC) belong to a group of bone matrix-associated factors that mediate cellmatrix interactions but do not serve primarily structural roles [3, 4]. Both proteins are normally expressed when tissue undergoes events that affect changes in cell-matrix or cell-cell interaction such as tissue renewal or remodeling and embryogenic development [5]. The deposition of hydroxyapatite in bone tissue requires the coordinated expression of a number of molecules including OPN and SPARC in cells of osteoblastic lineage [6]
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