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Clinical Investigation pp 1–6Cite as

Prognostic Value of Osteoprotegerin and sRANKL in Bronchoalveolar Lavage Fluid of Patients with Advanced Non-small Cell Lung Cancer

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Part of the book series: Advances in Experimental Medicine and Biology ((NR,volume 1047))

Abstract

Osteoprotegerin (OPG) is a soluble decoy receptor for receptor activator of nuclear factor-kappa B ligand (sRANKL). OPG promotes endothelial cell survival and neoangiogenesis. Dysregulation of the OPG/RANKL system has been detected in several tumors. In the present study, we evaluated the clinical usefulness of OPG and sRANKL assessment in bronchoalveolar lavage fluid (BALF) of patients with advanced non-small cell lung cancer (NSCLC). We measured the concentration of OPG and sRANKL in BALF of 44 NSCLC patients and 15 healthy volunteers taken as control subjects. The OPG content was higher in the NSCLC group than that in controls [0.48 (0.12–1.45) vs. 0.23 (0.14–0.75) pmol/l; p = 0.0001]. There were no significant differences in sRANKL content between the NSCLC and control groups [1.22 (0.74–23.00) vs. 1.12 (0.79–4.39) pmol/l; p = 0.67]. However, we found that the greater the level of sRANKL in NSCLC patients, the shorter the overall survival. We found a correlation between the content of sRANKL and the percentage of lymphocytes in BALF of NSCLC patients (r = 0.52; p = 0.041). We conclude that NSCLC patients have a higher content of OPG in BALF than healthy people. A high level of sRANKL in BALF of NSCLC patients may predict worse survival.

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References

  • Baud’huin M, Duplomb L, Teletchea S, Lamoureux F, Ruiz-Velasco C, Maillasson M, Redini F, Heymann MF, Heymann D (2013) Osteoprotegerin: multiple partners for multiples functions. Cytokine Growth Factor Rev 24:401–409

    Article  CAS  PubMed  Google Scholar 

  • Cathomas R, Rothermundt C, Bode B, Fuchs B, von Moos R, Schwitter M (2015) RANK ligand blockade with denosumab in combination with sorafenib in chemorefractory osteosarcoma: a possible step forward? Oncology 88:257–260

    Article  CAS  PubMed  Google Scholar 

  • Chansky K, Detterbeck FC, Nicholson AG, Rusch VW, Vallières E, Groome P, Kennedy C, Krasnik M, Peake M, Shemanski L, Bolejack V, Crowley JJ, Asamura H, Rami-Porta R, Staging IASLC, Prognostic Factors Committee, Advisory Boards, and Participating Institutions (2017) The IASLC lung cancer staging project: external validation of the revision of the TNM stage groupings in the eighth edition of the TNM classification of lung cancer. J Thorac Oncol 12(7):1109–1121

    Article  PubMed  Google Scholar 

  • Chen G, Sircar K, Aprikian A, Potti A, Goltzman D, Rabbani SA (2006) Expression of RANKL/RANK/OPG in primary and metastatic human prostate cancer as markers of disease stage and functional regulation. Cancer 107:289–298

    Article  CAS  PubMed  Google Scholar 

  • Cross SS, Yang Z, Brown NJ, Balasubramanian SP, Evans CA, Woodward JK, Neville-Webbe HL, Lippitt JM, Reed MW, Coleman RE, Holen I (2006) Osteoprotegerin (OPG) – a potential new role in the regulation of endothelial cell phenotype and tumour angiogenesis? Int J Cancer 118:1901–1908

    Article  CAS  PubMed  Google Scholar 

  • De Toni EN, Thieme SE, Herbst A, Behrens A, Stieber P, Jung A, Blum H, Göke B, Kolligs FT (2008) OPG is regulated by beta-catenin and mediates resistance to TRAIL-induced apoptosis in colon cancer. Clin Cancer Res 14:4713–4718

    Article  PubMed  Google Scholar 

  • Emery JG, McDonnell P, Burke MB, Deen KC, Lyn S, Silverman C, Dul E, Appelbaum ER, Eichman C, DiPrinzio R, Dodds RA, James IE, Rosenberg M, Lee JC, Young PR (1998) Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL. J Biol Chem 273:14363–14367

    Article  CAS  PubMed  Google Scholar 

  • Gonda TA, Tu S, Wang TC (2009) Chronic inflammation, the tumor microenvironment and carcinogenesis. Cell Cycle 8:2005–2013

    Article  CAS  PubMed  Google Scholar 

  • Holen I, Shipman CM (2006) Role of osteoprotegerin (OPG) in cancer. Clin Sci 110:279–291

    Article  CAS  PubMed  Google Scholar 

  • Holen I, Croucher PI, Hamdy FC, Eaton CL (2002) Osteoprotegerin (OPG) is a survival factor for human prostate cancer cells. Cancer Res 62:1619–1623

    PubMed  CAS  Google Scholar 

  • Holen I, Cross SS, Neville-Webbe HL, Cross NA, Balasubramanian SP, Croucher PI, Evans CA, Lippitt JM, Coleman RE, Eaton CL (2005) Osteoprotegerin (OPG) expression by breast cancer cells in vitro and breast tumours in vivo—a role in tumour cell survival? Breast Cancer Res Treat 92:207–215

    Article  CAS  PubMed  Google Scholar 

  • Karapanagiotou EM, Terpos E, Dilana KD, Alamara C, Gkiozos I, Polyzos A, Syrigos KN (2010) Serum bone turnover markers may be involved in the metastatic potential of lung cancer patients. Med Oncol 27:332–338

    Article  CAS  PubMed  Google Scholar 

  • Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, Hsu H, Sullivan J, Hawkins N, Davy E, Capparelli C, Eli A, Qian YX, Kaufman S, Sarosi I, Shalhoub V, Senaldi G, Guo J, Delaney J, Boyle WJ (1998) Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93:165–176

    Article  CAS  Google Scholar 

  • Lee JA, Jung JS, Kim DH, Lim JS, Kim MS, Kong CB, Song WS, Cho WH, Jeon DG, Lee SY, Koh JS (2011) RANKL expression is related to treatment outcome of patients with localized, high-grade osteosarcoma. Pediatr Blood Cancer 56:738–743

    Article  PubMed  Google Scholar 

  • Lu C, Sun C, Jin H (2016) Serum sRANKL and sRANKL/OPG ratio: novel biomarkers in non-small cell lung cancer. Oncol Lett 11:2261–2265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Peng X, Guo W, Ren T, Lou Z, Lu X, Zhang S, Lu Q, Sun Y (2013) Differential expression of the RANKL/RANK/OPG system is associated with bone metastasis in human non-small cell lung cancer. PLoS One 8:58361

    Article  CAS  Google Scholar 

  • Renema N, Navet B, Heymann MF, Lezot F, Heymann D (2016) RANK-RANKL signalling in cancer. Biosci Rep 36(4). https://doi.org/10.1042/BSR20160150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roux S, Amazit L, Meduri G, Guiochon-Mantel A, Milgrom E, Mariette X (2002) RANK (receptor activator of nuclear factor kappa B) and RANK ligand are expressed in giant cell tumors of bone. Am J Clin Pathol 117:210–216

    Article  CAS  PubMed  Google Scholar 

  • Theoleyre S, Wittrant Y, KwanTat S, Fortun Y, Redini F, Heymann DT (2004) The molecular triad OPG/RANK/RANKL: involvement in the orchestration of pathophysiological bone remodeling. Cytokine Growth Factor Rev 15:457–475

    Article  CAS  PubMed  Google Scholar 

  • Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG (2000) New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 92:205–216

    Article  CAS  PubMed  Google Scholar 

  • Travis WD, Brambilla E, Müller-Hermelink HK, Harris CC (2004) Pathology and genetics of tumours of the lung, pleura, thymus and heart, World Health Organization classification of tumours. ARC Press, Lyon, pp 10–33

    Google Scholar 

  • Woodard GA, Jones KD, Jablons DM (2016) Lung cancer staging and prognosis. Cancer Treat Res 170:47–75

    Article  PubMed  Google Scholar 

  • Zang L, Ma M, Hu J, Qiu H, Huang B, Chu T (2015) The effects of lung and prostate cancer bone metastasis on serum osteoprotegerin levels: a meta-analysis. Sci Rep 16:18324

    Google Scholar 

Download references

Conflicts of Interest

The authors had no conflicts of interest to declare in relation to this article.

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Authors and Affiliations

  1. First Department of Lung Diseases and Chemotherapy of Respiratory Neoplasms, Medical University of Bialystok, 14 Zurawia Street, PL 15-54, Bialystok, Poland

    W. Naumnik & M. Ossolińska

  2. Department of Clinical Molecular Biology, Medical University of Bialystok, Bialystok, Poland

    W. Naumnik & J. Nikliński

  3. Municipal Hospital, Bialystok, Poland

    I. Płońska

  4. First Department of Nephrology and Transplantation with Dialysis Unit, Medical University of Bialystok, Bialystok, Poland

    B. Naumnik

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  1. W. Naumnik
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  2. I. Płońska
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  3. M. Ossolińska
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  4. J. Nikliński
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  5. B. Naumnik
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Correspondence to W. Naumnik .

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Editors and Affiliations

  1. Opole Medical School, Opole, Poland

    Mieczyslaw Pokorski

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Naumnik, W., Płońska, I., Ossolińska, M., Nikliński, J., Naumnik, B. (2017). Prognostic Value of Osteoprotegerin and sRANKL in Bronchoalveolar Lavage Fluid of Patients with Advanced Non-small Cell Lung Cancer. In: Pokorski, M. (eds) Clinical Investigation. Advances in Experimental Medicine and Biology(), vol 1047. Springer, Cham. https://doi.org/10.1007/5584_2017_111

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