Serum Level of Osteopontin as a Prognostic Factor in Patients Who Underwent Surgical Resection for Non–Small-Cell Lung Cancer

Published:November 02, 2012DOI:



      OPN is a multifunctional glycophosphoprotein originally described as a secreted protein from malignant epithelial cells. This study focused on the clinical significance of preoperative serum level of OPN in NSCLC patients who underwent a complete resection.

      Patients and Methods

      The serum OPN level was assayed in 244 patients who underwent a complete resection of NSCLC by commercially available sandwich enzyme-linked immunosorbent assay kits. The patients were considered as a higher group, when the serum OPN levels exceeded 81.3 ng/mL.


      The patients included 166 male and 78 female subjects. The histologic types included 172 adenocarcinomas, 49 squamous cell carcinomas, and 23 other types of carcinoma. The serum level of OPN in male patients (92.6 ng/mL) was significantly higher than that of female patients (76.9 ng/mL). The OPN level of squamous cell carcinoma was significantly higher than that of adenocarcinoma. The OPN level was significantly elevated in patients with the pleural invasion or microvascular invasion than those without the invasion. The 5-year survival rate after surgery in the lower OPN group (82.0%) was a significant favorable prognosis than that in the higher OPN group (63.7%) (P < .0001). The 5-year survival rates in the lower OPN group at stage I NSCLC (88.1%) was significantly better than that in the higher OPN group (80.5%) (P = .0321).


      The preoperative serum OPN level was a useful predictor of an unfavorable prognosis, and it was found to be an independent prognostic determinant of outcome in patients who underwent surgery for NSCLC.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Clinical Lung Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Jemal A.
        • Siegel R.
        • Xu J.
        • et al.
        Cancer statistics.
        CA Cancer J Clin. 2010; 60: 277-300
        • Ferlay J.
        • Shin H.R.
        • Bray F.
        • et al.
        Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008.
        Int J Cancer. 2010; 127: 2893-2917
        • Spiro S.G.
        • Silvestri G.A.
        One hundred years of lung cancer.
        Am J Respir Crit Care Med. 2005; 172: 523-529
        • Ou S.H.
        • Zell J.A.
        Validation study of the proposed IASLC staging revisions of the T4 and M non-small cell lung cancer descriptors using data from 23,583 patients in the California cancer registry.
        J Thorac Oncol. 2008; 3: 216-227
        • Asamura H.
        • Goya T.
        • Koshiishi Y.
        • et al.
        A Japanese lung cancer registry study: prognosis of 13,010 resected lung cancers.
        J Thorac Oncol. 2008; 3: 46-52
        • Hanagiri T.
        • Baba T.
        • So T.
        • et al.
        Time trends of surgical outcome in patients with non-small cell lung cancer.
        J Thorac Oncol. 2010; 5: 825-829
        • Douillard J.Y.
        • Rosell R.
        • De Lena M.
        • et al.
        Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial.
        Lancet Oncol. 2006; 7: 719-727
        • Pignon J.P.
        • Tribodet H.
        • Scagliotti G.V.
        • et al.
        Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group.
        J Clin Oncol. 2008; 26: 3552-3559
        • Denhardt D.T.
        • Guo X.
        Osteopontin: a protein with diverse functions.
        FASEB J. 1993; 7: 1475-1482
        • Bellahcène A.
        • Castronovo V.
        Increased expression of osteonectin and osteopontin, two bone matrix proteins, in human breast cancer.
        Am J Pathol. 1995; 146: 95-100
        • Coppola D.
        • Szabo M.
        • Boulware D.
        • et al.
        Correlation of osteopontin protein expression and pathological stage across a wide variety of tumor histologies.
        Clin Cancer Res. 2004; 10: 184-190
        • Hu Z.
        • Lin D.
        • Yuan J.
        • et al.
        Overexpression of osteopontin is associated with more aggressive phenotypes in human non-small cell lung cancer.
        Clin Cancer Res. 2005; 11: 4646-4652
        • Donati V.
        • Boldrini L.
        • Dell'Omodarme M.
        • et al.
        Osteopontin expression and prognostic significance in non-small cell lung cancer.
        Clin Cancer Res. 2005; 11: 6459-6465
        • Goldstraw P.
        • Crowley J.
        • Chansky K.
        • et al.
        The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumours.
        J Thorac Oncol. 2007; 2: 706-714
      1. Travis W.D. Colby T.V. Corrin B. Histological Type of Lung and Pleural Tumors. World Health Organization International Histological Classification of Tumors. 3rd edition. Springer, Berlin1999
        • Hanagiri T.
        • Takenaka M.
        • Oka S.
        • et al.
        Prognostic significance of lymphovascular invasion for patients with stage I non-small cell lung cancer.
        Eur Surg Res. 2011; 47: 211-217
        • Nakagawa M.
        • Tanaka F.
        • Tsubota N.
        • et al.
        A randomized phase III trial of adjuvant chemotherapy with UFT for completely resected pathological stage I non-small-cell lung cancer: the West Japan Study Group for Lung Cancer Surgery (WJSG)–the 4th study.
        Ann Oncol. 2005; 16: 75-80
        • Guldur M.E.
        • Kibar Y.
        • Deniz H.
        • et al.
        Comparison of osteopontin, beta-catenin and hnRNP B1 expression in lung carcinomas.
        Pathol Oncol Res. 2010; 16: 55-59
        • Zhang J.
        • Takahashi K.
        • Takahashi F.
        • et al.
        Differential osteopontin expression in lung cancer.
        Cancer Lett. 2001; 171: 215-222
        • Le Q.T.
        • Sutphin P.D.
        • Raychaudhuri S.
        • et al.
        Identification of osteopontin as a prognostic plasma marker for head and neck squamous cell carcinomas.
        Clin Cancer Res. 2003; 9: 59-67
        • Rudland P.S.
        • Platt-Higgins A.
        • El-Tanani M.
        • et al.
        Prognostic significance of the metastasis-associated protein osteopontin in human breast cancer.
        Cancer Res. 2002; 62: 3417-3427
        • Agrawal D.
        • Chen T.
        • Irby R.
        • et al.
        Osteopontin identified as lead marker of colon cancer progression, using pooled sample expression profiling.
        J Natl Cancer Inst. 2002; 94: 513-521
        • Isa S.
        • Kawaguchi T.
        • Teramukai S.
        • et al.
        Serum osteopontin levels are highly prognostic for survival in advanced non-small cell lung cancer: results from JMTO LC 0004.
        J Thorac Oncol. 2009; 4: 1104-1110
        • Mack P.C.
        • Redman M.W.
        • Chansky K.
        • et al.
        Lower osteopontin plasma levels are associated with superior outcomes in advanced non-small-cell lung cancer patients receiving platinum-based chemotherapy: SWOG Study S0003.
        J Clin Oncol. 2008; 26: 4771-4776
        • Blasberg J.D.
        • Pass H.I.
        • Goparaju C.M.
        • et al.
        Reduction of elevated plasma osteopontin levels with resection of non-small-cell lung cancer.
        J Clin Oncol. 2010; 28: 936-941
        • Liaw L.
        • Skinner M.P.
        • Raines E.W.
        • et al.
        The adhesive and migratory effects of osteopontin are mediated via distinct cell surface integrins.
        J Clin Invest. 1995; 95: 713-724
        • Katagiri Y.U.
        • Sleeman J.
        • Fujii H.
        • et al.
        CD44 variants but not CD44s cooperate with beta1-containing integrins to permit cells to bind to osteopontin independently of arginine-glycine-aspartic acid, thereby stimulating cell motility and chemotaxis.
        Cancer Res. 1999; 59: 219-226
        • Tuck A.B.
        • Arsenault D.M.
        • O'Malley F.P.
        • et al.
        Osteopontin induces increased invasiveness and plasminogen activator expression of human mammary epithelial cells.
        Oncogene. 1999; 18: 4237-4246
        • Desai B.
        • Rogers M.J.
        • Chellaiah M.A.
        Mechanisms of osteopontin and CD44 as metastatic principles in prostate cancer cells.
        Mol Cancer. 2007; 6: 18
        • Liu H.
        • Chen A.
        • Guo F.
        • et al.
        A short-hairpin RNA targeting osteopontin downregulates MMP-2 and MMP-9 expressions in prostate cancer PC-3 cells.
        Cancer Lett. 2010; 295: 27-37
        • Shojaei F.
        • Scott N.
        • Kang X.
        • et al.
        Osteopontin induces growth of metastatic tumors in a preclinical model of non-small lung cancer.
        J Exp Clin Cancer Res. 2012; 31: 26