Osteopontin is a prognostic biomarker in non-small cell lung cancer

Ane Kongsgaard Rud,Marius Lund-Iversen,Miriam Øijordsbakken,Gunhild M Mælandsmo,Odd Terje Brustugun,Åslaug Helland,Gisle Berge,Steinar K Solberg,Kjetil Boye,Ann Rita Halvorsen

doi:10.1186/1471-2407-13-540

Ane Kongsgaard Rud, Marius Lund-Iversen + Show 8 more

Open Access

https://doi.org/10.1186/1471-2407-13-540

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Abstract

BackgroundIn a previously published report we characterized the expression of the metastasis-associated proteins S100A4, osteopontin (OPN) and ephrin-A1 in a prospectively collected panel of non-small cell lung cancer (NSCLC) tumors. The aim of the present follow-up study was to investigate the prognostic impact of these potential biomarkers in the same patient cohort. In addition, circulating serum levels of OPN were measured and single nucleotide polymorphisms (SNP) in the -443 position of the OPN promoter were analyzed.MethodsAssociations between immunohistochemical expression of S100A4, OPN and ephrin-A1 and relapse free and overall survival were examined using univariate and multivariate analyses. Serum OPN was measured by ELISA, polymorphisms in the -443 position of the tumor OPN promoter were analyzed by PCR, and associations between OPN levels and promoter polymorphisms and clinicopathological parameters and patient outcome were investigated.ResultsHigh expression of OPN in NSCLC tumors was associated with poor patient outcome, and OPN was a strong, independent prognostic factor for both relapse free and overall survival. Serum OPN levels increased according to tumor pT classification and tumor size, and patients with OPN-expressing tumors had higher serum levels than patients with OPN-negative tumors. S100A4 was a negative prognostic factor in several subgroups of adenocarcinoma patients, but not in the overall patient cohort. There was no association between ephrin-A1 expression and patient outcome.ConclusionsOPN is a promising prognostic biomarker in NSCLC, and should be further explored in the selection of patients for adjuvant treatment following surgical resection.

Highlights

In a previously published report we characterized the expression of the metastasis-associated proteins S100A4, osteopontin (OPN) and ephrin-A1 in a prospectively collected panel of non-small cell lung cancer (NSCLC) tumors
In our previously published report we showed that S100A4, OPN and ephrin-A1 were highly expressed in NSCLC tumor tissue, and that S100A4 expression was associated with adenocarcinoma histology, as well as with small tumor size and high degree of differentiation
S100A4, OPN and ephrin-A1 are all potentially interesting biomarkers that may have clinical impact in NSCLC, and in this follow-up study we investigate the association between the expression of these proteins and patient outcome in the previously described cohort

Summary

Introduction

In a previously published report we characterized the expression of the metastasis-associated proteins S100A4, osteopontin (OPN) and ephrin-A1 in a prospectively collected panel of non-small cell lung cancer (NSCLC) tumors. The overall 5-year survival rate for NSCLC is poor, and even for patients with early stage disease who undergo curatively intended surgery, the post operative recurrence rate is high compared to other types of cancer [2]. In a prospectively collected panel of tumor tissue from 244 NSCLC patients undergoing curatively intended surgery, we have previously characterized the expression of the metastasis-associated proteins S100A4, osteopontin (OPN) and ephrin-A1, and investigated the associations between these proteins and clinical and histopathological parameters [4]. Circulating plasma OPN levels in NSCLC patients have been shown to correlate with disease stage [16,18] and with survival [19,20]. OPN can undergo extensive post-translational modifications and alternative RNA splicing [11], and polymorphisms in the OPN promoter have been shown to affect its transcriptional activity [18,21]

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