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Prognostic role of high sensitivity C-reactive protein and interleukin-6 in glioma and meningioma patients

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Abstract

High sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) can be important prognostic indicators of brain tumor patients. We investigated the association of circulating IL-6 and hsCRP concentrations with discharge outcomes and survival of glioma and meningioma patients. One-hundred and sixty-three (115 women; median age 57 years) patients admitted for meningioma (n = 94), high-grade glioma (n = 48) and low-grade glioma (n = 21) surgery were enrolled in this prospective cohort study. Serum samples were collected within 24 h of admission. Discharge outcome was evaluated using the Glasgow Outcome Scale (unfavorable outcome = score from 1 to 3). Follow-up continued until November, 2016. Elevated IL-6 (≥ 2 pg/ml) and hsCRP (≥ 1 mg/l) concentrations were present in 25 and 35% of brain tumor patients, respectively. Elevated IL-6 concentrations were associated with unfavorable outcome at hospital discharge, adjusting for brain tumor histological diagnosis, patient age and gender (OR 2.39, 95% CI 0.97–5.91, p = 0.05). Elevated hsCRP concentrations were not associated with discharge outcome (p = 0.13). In multivariate Cox regression analyses adjusted for patient age, gender, extent of tumor resection and adjuvant treatment, elevated IL-6 concentration was associated with greater mortality risk in high-grade glioma patients (OR 2.623; 95% CI 1.129–5.597; p = 0.01), while elevated hsCRP concentration was associated with greater mortality risk in meningioma patients (OR 3.650; 95% CI 1.038–12.831; p = 0.04). Elevated IL-6 concentration is associated with greater unfavorable outcome risk in brain tumor patients and with greater mortality in high-grade glioma patients, while elevated hsCRP concentration is associated with greater mortality in meningioma patients.

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References

  1. Ostrom QT, Gittleman H, Xu J et al (2016) CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2009–2013. Neuro Oncol 18(suppl_5):v1–v75. https://doi.org/10.1093/neuonc/now207

    Article  Google Scholar 

  2. Wegman-Ostrosky T, Reynoso-Noverón N, Mejía-Pérez SI et al (2016) Clinical prognostic factors in adults with astrocytoma: Historic cohort. Clin Neurol Neurosurg 146:116–122. https://doi.org/10.1016/j.clineuro.2016.05.002

    Article  PubMed  Google Scholar 

  3. McGirt MJ, Chaichana KL, Gathinji M et al (2009) Independent association of extent of resection with survival in patients with malignant brain astrocytoma. J Neurosurg 110(1):156–162. https://doi.org/10.3171/2008.4.17536

    Article  PubMed  Google Scholar 

  4. Mukherjee S, Thakur B, Corns R et al (2015) Resection of olfactory groove meningioma - a review of complications and prognostic factors. Br J Neurosurg 29(5):685–692. https://doi.org/10.3109/02688697.2015.1054348

    Article  PubMed  Google Scholar 

  5. van Alkemade H, de Leau M, Dieleman EMT et al (2012) Impaired survival and long-term neurological problems in benign meningioma. Neuro Oncol 14(5):658–666. https://doi.org/10.1093/neuonc/nos013

    Article  PubMed  PubMed Central  Google Scholar 

  6. Christofides A, Kosmopoulos M, Piperi C (2015) Pathophysiological mechanisms regulated by cytokines in gliomas. Cytokine 71(2):377–384. https://doi.org/10.1016/j.cyto.2014.09.008

    Article  CAS  PubMed  Google Scholar 

  7. Gieryng A, Pszczolkowska D, Walentynowicz KA, Rajan WD, Kaminska B (2017) Immune microenvironment of gliomas. Lab Investig 97(5):498–518. https://doi.org/10.1038/labinvest.2017.19

    Article  CAS  PubMed  Google Scholar 

  8. Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S (2011) The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta 1813(5):878–888. https://doi.org/10.1016/j.bbamcr.2011.01.034

    Article  CAS  PubMed  Google Scholar 

  9. Chang C-Y, Li M-C, Liao S-L, Huang Y-L, Shen C-C, Pan H-C (2005) Prognostic and clinical implication of IL-6 expression in glioblastoma multiforme. J Clin Neurosci 12(8):930–933. https://doi.org/10.1016/j.jocn.2004.11.017

    Article  CAS  PubMed  Google Scholar 

  10. Todo T, Adams EF, Rafferty B, Fahlbusch R, Dingermann T, Werner H (1994) Secretion of interleukin-6 by human meningioma cells: possible autocrine inhibitory regulation of neoplastic cell growth. J Neurosurg 81(3):394–401. https://doi.org/10.3171/jns.1994.81.3.0394

    Article  CAS  PubMed  Google Scholar 

  11. Jones TH, Justice SK, Timperley WR, Royds JA (1997) Effects of interleukin-1 and dexamethasone on interleukin-6 production and growth in human meningiomas. J Pathol 183(4):460–468

    Article  CAS  PubMed  Google Scholar 

  12. Park K-J, Kang S-H, Chae Y-S et al (2010) Influence of interleukin-6 on the development of peritumoral brain edema in meningiomas. J Neurosurg 112(1):73–80. https://doi.org/10.3171/2009.4.JNS09158

    Article  CAS  PubMed  Google Scholar 

  13. Baumann H, Gauldie J (1994) The acute phase response. Immunol Today 15(2):74–80. https://doi.org/10.1016/0167-5699(94)90137-6

    Article  CAS  PubMed  Google Scholar 

  14. Aulin J, Siegbahn A, Hijazi Z et al (2015) Interleukin-6 and C-reactive protein and risk for death and cardiovascular events in patients with atrial fibrillation. Am Heart J 170(6):1151–1160. https://doi.org/10.1016/j.ahj.2015.09.018

    Article  CAS  PubMed  Google Scholar 

  15. Hedman A, Larsson PT, Alam M, Wallen NH, Nordlander R, Samad BA. CRP (2007) IL-6 and endothelin-1 levels in patients undergoing coronary artery bypass grafting. Do preoperative inflammatory parameters predict early graft occlusion and late cardiovascular events? Int J Cardiol 120(1):108–114. https://doi.org/10.1016/j.ijcard.2006.09.004

    Article  PubMed  Google Scholar 

  16. Kersten C, Louhimo J, Ålgars A et al (2013) Increased C-reactive protein implies a poorer stage-specific prognosis in colon cancer. Acta Oncol 52(8):1691–1698. https://doi.org/10.3109/0284186X.2013.835494

    Article  CAS  PubMed  Google Scholar 

  17. Licastro F, Hrelia S, Porcellini E et al (2016) Peripheral Inflammatory markers and antioxidant response during the post-acute and chronic phase after severe traumatic brain injury. Front Neurol 7:189. https://doi.org/10.3389/fneur.2016.00189

    Article  PubMed  PubMed Central  Google Scholar 

  18. Pusch G, Debrabant B, Molnar T et al (2015) Early dynamics of P-selectin and interleukin 6 predicts outcomes in ischemic stroke. J Stroke Cerebrovasc Dis 24(8):1938–1947. https://doi.org/10.1016/j.jstrokecerebrovasdis.2015.05.005

    Article  PubMed  Google Scholar 

  19. Patgiri D, Pathak MS, Sharma P, Kutum T, Mattack N (2014) Serum hsCRP: a novel marker for prediction of cerebrovascular accidents (stroke). J Clin Diagn Res 8(12):CC08-11. https://doi.org/10.7860/JCDR/2014/10386.5302

    PubMed  Google Scholar 

  20. Strojnik T, Smigoc T, Lah TT (2014) Prognostic value of erythrocyte sedimentation rate and C-reactive protein in the blood of patients with glioma. Anticancer Res 34(1):339–347

    PubMed  Google Scholar 

  21. Reynés G, Vila V, Martín M et al (2011) Circulating markers of angiogenesis, inflammation, and coagulation in patients with glioblastoma. J Neurooncol 102(1):35–41. https://doi.org/10.1007/s11060-010-0290-x

    Article  PubMed  Google Scholar 

  22. Jennett B, Bond M (1975) Assessment of outcome after severe brain damage. Lancet (London, England) 1(7905):480–484. http://www.ncbi.nlm.nih.gov/pubmed/46957. Accessed 4 Sept 2017

  23. Bunevicius A, Deltuva V, Tamasauskas S, Tamasauskas A, Laws ER, Bunevicius R (2013) Low triiodothyronine syndrome as a predictor of poor outcomes in patients undergoing brain tumor surgery: a pilot study: clinical article. J Neurosurg 118(6):1279–1287. https://doi.org/10.3171/2013.1.JNS121696

    Article  CAS  PubMed  Google Scholar 

  24. Iłzecka J, Iłzecki M (2006) APRIL is increased in serum of patients with brain glioblastoma multiforme. Eur Cytokine Netw 17(4):276–280

    PubMed  Google Scholar 

  25. Doroudchi M, Pishe ZG, Malekzadeh M, Golmoghaddam H, Taghipour M, Ghaderi A (2013) Elevated serum IL-17A but not IL-6 in glioma versus meningioma and schwannoma. Asian Pac J Cancer Prev 14(9):5225–5230

    Article  PubMed  Google Scholar 

  26. Kataki A, Skandami V, Memos N et al (2014) Similar immunity profiles in patients with meningioma and glioma tumors despite differences in the apoptosis and necrosis of circulating lymphocyte and monocyte populations. J Neurosurg Sci 58(1):9–15

    CAS  PubMed  Google Scholar 

  27. Demirci U, Yaman M, Buyukberber S et al (2012) Prognostic importance of markers for inflammation, angiogenesis and apoptosis in high grade glial tumors during temozolomide and radiotherapy. Int Immunopharmacol 14(4):546–549. https://doi.org/10.1016/j.intimp.2012.08.007

    Article  CAS  PubMed  Google Scholar 

  28. Kumar R, Kamdar D, Madden L et al (2006) Th1/Th2 cytokine imbalance in meningioma, anaplastic astrocytoma and glioblastoma multiforme patients. Oncol Rep 15(6):1513–1516

    CAS  PubMed  Google Scholar 

  29. Vignes JR, Sesay M, Rezajooi K, Gimbert E, Liguoro D (2008) Peritumoral edema and prognosis in intracranial meningioma surgery. J Clin Neurosci 15(7):764–768. https://doi.org/10.1016/j.jocn.2007.06.001

    Article  CAS  PubMed  Google Scholar 

  30. Schoenegger K, Oberndorfer S, Wuschitz B et al (2009) Peritumoral edema on MRI at initial diagnosis: an independent prognostic factor for glioblastoma? Eur J Neurol 16(7):874–878. https://doi.org/10.1111/j.1468-1331.2009.02613.x

    Article  CAS  PubMed  Google Scholar 

  31. Shan Y, He X, Song W, Han D, Niu J, Wang J (2015) Role of IL-6 in the invasiveness and prognosis of glioma. Int J Clin Exp Med 8(6):9114–9120

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Tchirkov A, Khalil T, Chautard E et al (2007) Interleukin-6 gene amplification and shortened survival in glioblastoma patients. Br J Cancer 96(3):474–476. https://doi.org/10.1038/sj.bjc.6603586

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Wang H, Lathia JD, Wu Q et al (2009) Targeting interleukin 6 signaling suppresses glioma stem cell survival and tumor growth. Stem Cells 27(10):2393–2404. https://doi.org/10.1002/stem.188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Kuo H-K, Yen C-J, Chang C-H, Kuo C-K, Chen J-H, Sorond F (2005) Relation of C-reactive protein to stroke, cognitive disorders, and depression in the general population: systematic review and meta-analysis. Lancet Neurol 4(6):371–380. https://doi.org/10.1016/S1474-4422(05)70099-5

    Article  CAS  PubMed  Google Scholar 

  35. Emerging Risk Factors Collaboration, Kaptoge S, Di Angelantonio E, et al (2010) C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet 375(9709):132–140. https://doi.org/10.1016/S0140-6736(09)61717-7

    Article  Google Scholar 

  36. Bunevicius A, Kazlauskas H, Raskauskiene N et al (2015) Role of N-terminal pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and inteleukin-6 in predicting a poor outcome after a stroke. Neuroimmunomodulation 22(6):365–372. https://doi.org/10.1159/000381218

    Article  CAS  PubMed  Google Scholar 

  37. Noble JM, Manly JJ, Schupf N, Tang MX, Mayeux R, Luchsinger JA (2010) Association of C-reactive protein with cognitive impairment. Arch Neurol 67(1):87–92. https://doi.org/10.1001/archneurol.2009.308

    Article  PubMed  PubMed Central  Google Scholar 

  38. Bunevicius A, Deltuva VP, Tamasauskas A (2017) Association of pre-operative depressive and anxiety symptoms with five-year survival of glioma and meningioma patients: a prospective cohort study. Oncotarget 8(34):57543–57551. https://doi.org/10.18632/oncotarget.15743

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Professor Robertas Bunevicius, MD, PhD (1958–2014) passed away before the study completion. He established the study concept and guided preparation of the study protocol.

Funding

The study was supported by the Research Council of Lithuania (Grant number: MIP-044/2015).

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Authors and Affiliations

  1. Neuroscience Institute and Department of Neurosurgery, Lithuanian University of Health Sciences, Eiveniu g. 2, 50009, Kaunas, Lithuania

    Adomas Bunevicius, Andrius Radziunas, Sarunas Tamasauskas, Arimantas Tamasauskas & Vytenis Deltuva

  2. Department of Neurosurgery, Brigham and Women’s Hospital, Boston, MA, USA

    Edwards R. Laws

  3. CNR - Institute of Clinical Physiology, Pisa, Italy

    Giorgio Iervasi

  4. Lithuanian University of Health Sciences, Kaunas, Lithuania

    Robertas Bunevicius

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  1. Adomas Bunevicius
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Correspondence to Adomas Bunevicius.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Bunevicius, A., Radziunas, A., Tamasauskas, S. et al. Prognostic role of high sensitivity C-reactive protein and interleukin-6 in glioma and meningioma patients. J Neurooncol 138, 351–358 (2018). https://doi.org/10.1007/s11060-018-2803-y

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