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BMC Cancer
Published in: BMC Cancer 1/2016

Open Access 01-12-2016 | Research article

Osteopontin and thrombospondin-1 play opposite roles in promoting tumor aggressiveness of primary resected non-small cell lung cancer

Authors: Mathieu Rouanne, Julien Adam, Aïcha Goubar, Angélique Robin, Caroline Ohana, Emilie Louvet, Jiemin Cormier, Olaf Mercier, Peter Dorfmüller, Soly Fattal, Vincent Thomas de Montpreville, Thierry Lebret, Philippe Dartevelle, Elie Fadel, Benjamin Besse, Ken André Olaussen, Christian Auclair, Jean-Charles Soria

Published in: BMC Cancer | Issue 1/2016

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Abstract

Background

Osteopontin (OPN) and thrombospondin-1 (TSP-1) are extracellular matrix proteins secreted by stromal and tumor cells. These proteins appear to have a key role in the tumor microenvironment for cancer development and metastasis. There is little information regarding the prognostic value of the combination of these two proteins in human cancers. Our aim was to clarify clinical significance and prognostic value of each circulating protein and their combination in primary resected non-small cell lung cancer (NSCLC) patients.

Methods

We retrospectively reviewed 171 patients with NSCLC following curative intent surgery from January to December of 2012. Preoperative serums, demographics, clinical and pathological data and molecular profiling were analyzed. Pre-treatment OPN and TSP-1 serum levels were measured by ELISA. Tissue protein expression in primary tumor samples was determined by immunohistochemical analysis.

Results

OPN and TSP-1 serum levels were inversely correlated with survival rates. For each 50 units increment of serum OPN, an increased risk of metastasis by 69 % (unadjusted HR 1.69, 95 % CI 1.12–2.56, p = 0.01) and an increased risk of death by 95 % (unadjusted HR 1.95, 95 % CI 1.15–3.32, p = 0.01) were observed. Conversely, for each 10 units increment in TSP-1, the risk of death was decreased by 85 % (unadjusted HR 0.15, 95 % CI 0.03–0.89; p = 0.04). No statistically significant correlation was found between TSP-1 serum level and distant metastasis-free survival (p = 0.2). On multivariate analysis, OPN and TSP-1 serum levels were independent prognostic factors of overall survival (HR 1.71, 95 % CI 1.04–2.82, p = 0.04 for an increase of 50 ng/mL in OPN; HR 0.18, 95 % CI 0.04–0.87, p = 0.03 for an increase of 10 ng/mL in TSP-1). In addition, the combination of OPN and TSP-1 serum levels remained an independent prognostic factor for overall survival (HR 1.31, 95 % CI 1.03–1.67, p = 0.03 for an increase of 6 ng/mL in OPN/TSP-1 ratio).

Conclusions

Our results show that pre-treatment OPN and TSP-1 serum levels may reflect the aggressiveness of the tumor and might serve as prognostic markers in patients with primary resected NSCLC.
Appendix
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Metadata
Title
Osteopontin and thrombospondin-1 play opposite roles in promoting tumor aggressiveness of primary resected non-small cell lung cancer
Authors
Mathieu Rouanne
Julien Adam
Aïcha Goubar
Angélique Robin
Caroline Ohana
Emilie Louvet
Jiemin Cormier
Olaf Mercier
Peter Dorfmüller
Soly Fattal
Vincent Thomas de Montpreville
Thierry Lebret
Philippe Dartevelle
Elie Fadel
Benjamin Besse
Ken André Olaussen
Christian Auclair
Jean-Charles Soria
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2016
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-016-2541-5

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