Evaluation of Serum Ferritin Levels in Brain Tumors

Authors

  • Oana Alexandru University of Medicine and Pharmacy of Craiova
  • Laurentiu Ene University of Medicine and Pharmacy of Craiova

DOI:

https://doi.org/10.52701/monc.2021.v2i1.18

Keywords:

brain tumors, ferritin, iron metabolism

Abstract

Currently, brain tumors are diagnosed based on clinical suspicion and neuroimaging results. Histological analysis is the only method that certifies the diagnosis and establishes the prognosis. A number of studies suggest that perturbed iron metabolism and increased ferritin levels are part of the changes associated with tumorigenesis. Our study’s aim is to evaluate serum ferritin levels in a series of patients and establish if this protein could play a role in brain cancer diagnosis and prognosis. Our lot is comprised of 267 patients with various types of brain tumors. We registered higher mean ferritin levels when compared to the general population. According to tumor histology, higher levels were found in cerebral metastases patients, and the differences were statistically significant. According to tumor grading, we found higher ferritin levels in grade II tumors, with statistically significant differences when compared to grade I and grade IV tumors. It remains an open question if high ferritin levels are a hallmark for cerebral metastases or just an expression of systemic dissemination. Also, a possible role for ferritin as a biomarker in grade II brain tumors may be established by further studies.

Author Biography

Laurentiu Ene, University of Medicine and Pharmacy of Craiova

Department of Neurology

References

Dolecek TA, Propp JM, Stroup NE, Kruchko C. CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2005-2009. Neuro-oncology. 2012 Nov;14 Suppl 5:v1-49.

https://doi.org/10.1093/neuonc/nos218

Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta neuropathologica. 2016 Jun;131(6):803-20.

https://doi.org/10.1007/s00401-016-1545-1

Crichton R. Iron metabolism: from molecular mechanisms to clinical consequences: John Wiley & Sons; 2016.

https://doi.org/10.1002/9781118925645

Dizdaroglu M, Jaruga P. Mechanisms of free radical-induced damage to DNA. Free radical research. 2012 Apr;46(4):382-419.

https://doi.org/10.3109/10715762.2011.653969

Nelson RL. Iron and colorectal cancer risk: human studies. Nutrition reviews. 2001 May;59(5):140-8.

https://doi.org/10.1111/j.1753-4887.2001.tb07002.x

Bandera EV, Kushi LH, Moore DF, Gifkins DM, McCullough ML. Consumption of animal foods and endometrial cancer risk: a systematic literature review and meta-analysis. Cancer causes & control : CCC. 2007 Nov;18(9):967-88.

https://doi.org/10.1007/s10552-007-9038-0

Choi JY, Neuhouser ML, Barnett MJ, Hong CC, Kristal AR, Thornquist MD, et al. Iron intake, oxidative stress-related genes (MnSOD and MPO) and prostate cancer risk in CARET cohort. Carcinogenesis. 2008 May;29(5):964-70.

https://doi.org/10.1093/carcin/bgn056

Hong CC, Ambrosone CB, Ahn J, Choi JY, McCullough ML, Stevens VL, et al. Genetic variability in iron-related oxidative stress pathways (Nrf2, NQ01, NOS3, and HO-1), iron intake, and risk of postmenopausal breast cancer. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2007 Sep;16(9):1784-94.

https://doi.org/10.1158/1055-9965.EPI-07-0247

Bradbear RA, Bain C, Siskind V, Schofield FD, Webb S, Axelsen EM, et al. Cohort study of internal malignancy in genetic hemochromatosis and other chronic nonalcoholic liver diseases. Journal of the National Cancer Institute. 1985 Jul;75(1):81-4.

Osborne NJ, Gurrin LC, Allen KJ, Constantine CC, Delatycki MB, McLaren CE, et al. HFE C282Y homozygotes are at increased risk of breast and colorectal cancer. Hepatology. 2010 Apr;51(4):1311-8.

https://doi.org/10.1002/hep.23448

Daniels TR, Bernabeu E, Rodriguez JA, Patel S, Kozman M, Chiappetta DA, et al. The transferrin receptor and the targeted delivery of therapeutic agents against cancer. Biochimica et biophysica acta. 2012 Mar;1820(3):291-317.

https://doi.org/10.1016/j.bbagen.2011.07.016

Kakhlon O, Gruenbaum Y, Cabantchik ZI. Ferritin expression modulates cell cycle dynamics and cell responsiveness to H-ras-induced growth via expansion of the labile iron pool. The Biochemical journal. 2002 May 1;363(Pt 3):431-6.

https://doi.org/10.1042/bj3630431

Pinnix ZK, Miller LD, Wang W, D'Agostino R, Jr., Kute T, Willingham MC, et al. Ferroportin and iron regulation in breast cancer progression and prognosis. Science translational medicine. 2010 Aug 4;2(43):43ra56.

https://doi.org/10.1126/scitranslmed.3001127

Crichton RR, Declercq JP. X-ray structures of ferritins and related proteins. Biochimica et biophysica acta. 2010 Aug;1800(8):706-18.

https://doi.org/10.1016/j.bbagen.2010.03.019

Alkhateeb AA, Han B, Connor JR. Ferritin stimulates breast cancer cells through an iron-independent mechanism and is localized within tumor-associated macrophages. Breast cancer research and treatment. 2013 Feb;137(3):733-44.

https://doi.org/10.1007/s10549-012-2405-x

Faniello MC, Di Sanzo M, Quaresima B, Baudi F, Di Caro V, Cuda G, et al. p53-mediated downregulation of H ferritin promoter transcriptional efficiency via NF-Y. The international journal of biochemistry & cell biology. 2008;40(10):2110-9.

https://doi.org/10.1016/j.biocel.2008.02.010

Kalluri R. EMT: when epithelial cells decide to become mesenchymal-like cells. The Journal of clinical investigation. 2009 Jun;119(6):1417-9.

https://doi.org/10.1172/JCI39675

Zhang KH, Tian HY, Gao X, Lei WW, Hu Y, Wang DM, et al. Ferritin heavy chain-mediated iron homeostasis and subsequent increased reactive oxygen species production are essential for epithelial-mesenchymal transition. Cancer research. 2009 Jul 1;69(13):5340-8.

https://doi.org/10.1158/0008-5472.CAN-09-0112

Coffman LG, Parsonage D, D'Agostino R, Jr., Torti FM, Torti SV. Regulatory effects of ferritin on angiogenesis. Proceedings of the National Academy of Sciences of the United States of America. 2009 Jan 13;106(2):570-5.

https://doi.org/10.1073/pnas.0812010106

Higgy NA, Salicioni AM, Russo IH, Zhang PL, Russo J. Differential expression of human ferritin H chain gene in immortal human breast epithelial MCF-10F cells. Molecular carcinogenesis. 1997 Dec;20(4):332-9.

https://doi.org/10.1002/(SICI)1098-2744(199712)20:4<332::AID-MC2>3.0.CO;2-L

Zupancic K, Blejec A, Herman A, Veber M, Verbovsek U, Korsic M, et al. Identification of plasma biomarker candidates in glioblastoma using an antibody-array-based proteomic approach. Radiology and oncology. 2014 Sep;48(3):257-66

https://doi.org/10.2478/raon-2014-0014

Sato Y, Honda Y, Asoh T, Oizumi K, Ohshima Y, Honda E. Cerebrospinal fluid ferritin in glioblastoma: evidence for tumor synthesis. Journal of neuro-oncology. 1998 Oct;40(1):47-50.

https://doi.org/10.1023/A:1006078521790

Hoelscher M, Richter N, Melle C, von Eggeling F, Schaenzer A, Nestler U. SELDI-TOF analysis of glioblastoma cyst fluid is an approach for assessing cellular protein expression. Neurological research. 2013 Dec;35(10):993-1001.

https://doi.org/10.1179/016164113X13756993777580

Graner MW, Alzate O, Dechkovskaia AM, Keene JD, Sampson JH, Mitchell DA, et al. Proteomic and immunologic analyses of brain tumor exosomes. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2009 May;23(5):1541-57.

https://doi.org/10.1096/fj.08-122184

Motaln H, Gruden K, Hren M, Schichor C, Primon M, Rotter A, et al. Human mesenchymal stem cells exploit the immune response mediating chemokines to impact the phenotype of glioblastoma. Cell transplantation. 2012;21(7):1529-45.

https://doi.org/10.3727/096368912X640547

Strojnik T, Smigoc T, Lah TT. Prognostic value of erythrocyte sedimentation rate and C-reactive protein in the blood of patients with glioma. Anticancer research. 2014 Jan;34(1):339-47.

Sato Y, Sato Y, Hayashi T, Shojima K, Kaji M. Cerebrospinal fluid ferritin in patients with central nervous system tumors. The Kurume medical journal. 1985;32(3):229-35.

https://doi.org/10.2739/kurumemedj.32.229

Sarkaria JN, Hu LS, Parney IF, Pafundi DH, Brinkmann DH, Laack NN, et al. Is the blood-brain barrier really disrupted in all glioblastomas? A critical assessment of existing clinical data. Neuro-oncology. 2018 Jan 22;20(2):184-91.

https://doi.org/10.1093/neuonc/nox175

Yang P. [Ultrastructural localization of ferritin in glioma]. Zhonghua yi xue za zhi. 1989 May;69(5):274-5, 20.

Downloads

Published

2021-05-25