title: Osteopontin and thrombospondin-1 play opposite roles in promoting tumor aggressiveness of primary resected non-small cell lung cancer.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: INSERM Unit U981, Gustave Roussy Cancer Campus, 114, rue Edouard Vaillant, 94805, Villejuif, France. rouanne.mathieu@gmail.com.|Université Paris Sud, Université Paris-Saclay, 94270, Le Kremlin-Bicêtre, France. rouanne.mathieu@gmail.com.|CNRS UMR 8113, Ecole Normale Supérieure de Cachan, Cachan, France. rouanne.mathieu@gmail.com.|Hôpital Foch, Université Versailles-Saint-Quentin-en-Yvelines, Université Paris-Saclay, 92150, Suresnes, France. rouanne.mathieu@gmail.com.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Rouanne
authors.affiliation: INSERM Unit U981, Gustave Roussy Cancer Campus, 114, rue Edouard Vaillant, 94805, Villejuif, France.|Université Paris Sud, Université Paris-Saclay, 94270, Le Kremlin-Bicêtre, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Adam
authors.affiliation: INSERM Unit U981, Gustave Roussy Cancer Campus, 114, rue Edouard Vaillant, 94805, Villejuif, France.
authors.forename: Aïcha
authors.initials: A
authors.lastname: Goubar
authors.affiliation: INSERM Unit U981, Gustave Roussy Cancer Campus, 114, rue Edouard Vaillant, 94805, Villejuif, France.
authors.forename: Angélique
authors.initials: A
authors.lastname: Robin
authors.affiliation: CNRS UMR 8113, Ecole Normale Supérieure de Cachan, Cachan, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Ohana
authors.affiliation: INSERM Unit U981, Gustave Roussy Cancer Campus, 114, rue Edouard Vaillant, 94805, Villejuif, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Louvet
authors.affiliation: INSERM Unit U981, Gustave Roussy Cancer Campus, 114, rue Edouard Vaillant, 94805, Villejuif, France.
authors.forename: Jiemin
authors.initials: J
authors.lastname: Cormier
authors.affiliation: Université Paris Sud, Université Paris-Saclay, 94270, Le Kremlin-Bicêtre, France.|Departement of Thoracic and Vascular Surgery, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France.|Thoracic Multidisciplinary Committee, Institut d'Oncologie Thoracique, Le Plessis-Robinson, France.
authors.forename: Olaf
authors.initials: O
authors.lastname: Mercier
authors.affiliation: Thoracic Multidisciplinary Committee, Institut d'Oncologie Thoracique, Le Plessis-Robinson, France.|Department of Pathology, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France.
authors.forename: Peter
authors.initials: P
authors.lastname: Dorfmüller
authors.affiliation: Department of Biology, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France.
authors.forename: Soly
authors.initials: S
authors.lastname: Fattal
authors.affiliation: Thoracic Multidisciplinary Committee, Institut d'Oncologie Thoracique, Le Plessis-Robinson, France.|Department of Pathology, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France.
authors.forename: Vincent Thomas
authors.initials: VT
authors.lastname: de Montpreville
authors.affiliation: Hôpital Foch, Université Versailles-Saint-Quentin-en-Yvelines, Université Paris-Saclay, 92150, Suresnes, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Lebret
authors.affiliation: Université Paris Sud, Université Paris-Saclay, 94270, Le Kremlin-Bicêtre, France.|Departement of Thoracic and Vascular Surgery, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France.|Thoracic Multidisciplinary Committee, Institut d'Oncologie Thoracique, Le Plessis-Robinson, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Dartevelle
authors.affiliation: Université Paris Sud, Université Paris-Saclay, 94270, Le Kremlin-Bicêtre, France.|Departement of Thoracic and Vascular Surgery, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France.|Thoracic Multidisciplinary Committee, Institut d'Oncologie Thoracique, Le Plessis-Robinson, France.
authors.forename: Elie
authors.initials: E
authors.lastname: Fadel
authors.affiliation: INSERM Unit U981, Gustave Roussy Cancer Campus, 114, rue Edouard Vaillant, 94805, Villejuif, France.|Thoracic Multidisciplinary Committee, Institut d'Oncologie Thoracique, Le Plessis-Robinson, France.|Department of Cancer Medicine, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Besse
authors.affiliation: INSERM Unit U981, Gustave Roussy Cancer Campus, 114, rue Edouard Vaillant, 94805, Villejuif, France.|Université Paris Sud, Université Paris-Saclay, 94270, Le Kremlin-Bicêtre, France.|Thoracic Multidisciplinary Committee, Institut d'Oncologie Thoracique, Le Plessis-Robinson, France.
authors.forename: Ken André
authors.initials: KA
authors.lastname: Olaussen
authors.affiliation: Université Paris Sud, Université Paris-Saclay, 94270, Le Kremlin-Bicêtre, France.|CNRS UMR 8113, Ecole Normale Supérieure de Cachan, Cachan, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Auclair
authors.affiliation: INSERM Unit U981, Gustave Roussy Cancer Campus, 114, rue Edouard Vaillant, 94805, Villejuif, France.|Université Paris Sud, Université Paris-Saclay, 94270, Le Kremlin-Bicêtre, France.|Thoracic Multidisciplinary Committee, Institut d'Oncologie Thoracique, Le Plessis-Robinson, France.|Drug Development Department (DITEP: Département d'Innnovations Thérapeutiques et Essais Précoces), Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Soria
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D053495:Osteopontin / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D019700:Thrombospondin 1 / Q000097:blood* / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C506895:SPP1 protein, human; D019700:Thrombospondin 1; C000611726:thrombospondin-1, human; D053495:Osteopontin
keywords: Circulating biomarker; Non-small cell lung cancer; Osteopontin; Thrombospondin-1; Tumor microenvironment