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Plasma tumor necrosis factor-α and C-reactive protein as biomarker for survival in head and neck squamous cell carcinoma

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Abstract

Purpose

Tumor TNM staging is the main basis for prognosis and treatment decision for head and neck squamous cell carcinoma (HNSCC) despite significant heterogeneity in terms of outcome among patients with the same clinical stage. In this study, a possible role of plasma interleukin-2 (IL-2), interleukin-6 (IL-6), granulocyte–macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) as biomarkers for survival of HNSCC patients was investigated.

Methods

In this prospective study, plasma levels of IL-2, IL-6, GM-CSF, TNF-α and CRP in patients (n = 100) and controls (n = 48) were analyzed.

Results

Significantly elevated levels of CRP and TNF-α (p < 0.001) were found in the patients. Combination of upregulated CRP and TNF-α in the patient plasma was significantly related to shorter patient survival, independent of clinical stage.

Conclusions

Our findings indicate that CRP and TNF-α might be suitable as biomarkers in combination with tumor TNM staging for predicting survival and individualized treatment of HNSCC patients. Plasma CRP and TNF-α analysis are simple, rapid, cost effective and suitable for clinical practice.

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References

  1. Airoldi L, Magagnotti C, Iannuzzi AR, Marelli C, Bagnati R, Pastorelli R, Colombi A, Santaguida S, Chiabrando C, Schiarea S, Fanelli R (2009) Effects of cigarette smoking on the human urinary proteome. Biochem Biophys Res Commun 381(3):397–402

  2. Balkwill F, Mantovani A (2001) Inflammation and cancer: back to Virchow? Lancet 357(9255):539–545

  3. Black S, Kushner I, Samols D (2004) C-reactive protein. J Biol Chem 279(47):48487–48490

  4. Bose A, Chakraborty T, Chakraborty K, Pal S, Baral R (2008) Dysregulation in immune functions is reflected in tumor cell cytotoxicity by peripheral blood mononuclear cells from head and neck squamous cell carcinoma patients. Cancer Immun 8:10

  5. Chen Z, Malhotra PS, Thomas GR, Ondrey FG, Duffey DC, Smith CW, Enamorado I, Yeh NT, Kroog GS, Rudy S, McCullagh L, Mousa S, Quezado M, Herscher LL, Van Waes C (1999) Expression of proinflammatory and proangiogenic cytokines in patients with head and neck cancer. Clin Cancer Res 5(6):1369–1379

  6. Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420(6917):860–867

  7. Feghali CA, Wright TM (1997) Cytokines in acute and chronic inflammation. Front Biosci 2:d12–d26

  8. Forastiere A, Koch W, Trotti A, Sidransky D (2001) Head and neck cancer. N Engl J Med 345(26):1890–1900

  9. Haddad RI, Shin DM (2008) Recent advances in head and neck cancer. N Engl J Med 359(11):1143–1154

  10. Heikkila K, Ebrahim S, Lawlor DA (2007) A systematic review of the association between circulating concentrations of C reactive protein and cancer. J Epidemiol Commun Health 61(9):824–833

  11. Hoffmann TK, Bier H, Whiteside TL (2004) Targeting the immune system: novel therapeutic approaches in squamous cell carcinoma of the head and neck. Cancer Immunol Immunother 53(12):1055–1067

  12. Hsiao SH, Lee MS, Lin HY, Su YC, Ho HC, Hwang JH, Lee CC, Hung SK (2009) Clinical significance of measuring levels of tumor necrosis factor-alpha and soluble interleukin-2 receptor in nasopharyngeal carcinoma. Acta Otolaryngol 129(12):1519–1523

  13. Laytragoon-Lewin N, Bahram F, Rutqvist LE, Turesson I, Lewin F (2011) Direct effects of pure nicotine, cigarette smoke extract, Swedish-type smokeless tobacco (Snus) extract and ethanol on human normal endothelial cells and fibroblasts. Anticancer Res 31(5):1527–1534

  14. Leemans CR, Braakhuis BJ, Brakenhoff RH (2011) The molecular biology of head and neck cancer. Nat Rev Cancer 11(1):9–22

  15. Lewin F, Norell SE, Johansson H, Gustavsson P, Wennerberg J, Biorklund A, Rutqvist LE (1998) Smoking tobacco, oral snuff, and alcohol in the etiology of squamous cell carcinoma of the head and neck: a population-based case-referent study in Sweden. Cancer 82(7):1367–1375

  16. Lu X, Qian CN, Mu YG, Li NW, Li S, Zhang HB, Li SW, Wang FL, Guo X, Xiang YQ (2011) Serum CCL2 and serum TNF-alpha–two new biomarkers predict bone invasion, post-treatment distant metastasis and poor overall survival in nasopharyngeal carcinoma. Eur J Cancer 47(3):339–346

  17. Malfertheiner P, Schutte K (2006) Smoking–a trigger for chronic inflammation and cancer development in the pancreas. Am J Gastroenterol 101(1):160–162

  18. Peter F, Wittekindt C, Finkensieper M, Kiehntopf M, Guntinas-Lichius O (2013) Prognostic impact of pretherapeutic laboratory values in head and neck cancer patients. J Cancer Res Clin Oncol 139(1):171–178

  19. Rapidis AD, Wolf GT (2009) Immunotherapy of head and neck cancer: current and future considerations. J Oncol 2009:346345

  20. Sobin LH, Wittekind C (eds) (2002) TNM classification of malignant tumors, 6th edn. New York, Wiley

  21. van der Schroeff MP, Steyerberg EW, Wieringa MH, Langeveld TP, Molenaar J, Baatenburg de Jong RJ (2012) Prognosis: a variable parameter: dynamic prognostic modeling in head and neck squamous cell carcinoma. Head Neck 34(1):34–41

  22. Young MR (2006) Protective mechanisms of head and neck squamous cell carcinomas from immune assault. Head Neck 28(5):462–470

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Acknowledgments

Grants were received from Futurum-Academy of HealthCare at Jönköping County Council (No. 307251, 144631, 151361) and Foundation of Clinical Cancer Research, Jönköping, Sweden (No. 110426-1). We would like to thank the patients and healthy controls for blood samples, Annette Nilsson Bowers, Egon Karlsson and David Lewin for practical help.

Conflict of interest

No potential conflict of interest was disclosed.

Author information

Correspondence to Bengt-Åke Andersson.

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Andersson, B., Lewin, F., Lundgren, J. et al. Plasma tumor necrosis factor-α and C-reactive protein as biomarker for survival in head and neck squamous cell carcinoma. J Cancer Res Clin Oncol 140, 515–519 (2014). https://doi.org/10.1007/s00432-014-1592-8

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Keywords

  • Head and neck squamous cell carcinoma
  • Biomarkers
  • Survival
  • CRP
  • TNF-α