Adipocyte-fatty Acid Binding Protein is Associated with Clinical Stage and Inflammatory Markers in Head and Neck Cancer Patients

Sanaa A. El-Benhawy^1, and Heba G. El-Sheredy²

¹Radiation Sciences Department, Medical Research Institute, Alexandria University, Alexandria, Egypt

²Cancer Management and Research Department, Medical Research Institute, Alexandria University, Alexandria, Egypt

Cite this paper:
Sanaa A. El-Benhawy and Heba G. El-Sheredy. Adipocyte-fatty Acid Binding Protein is Associated with Clinical Stage and Inflammatory Markers in Head and Neck Cancer Patients. Journal of Cancer Research and Treatment. 2016; 4(3):41-48. doi: 10.12691/jcrt-4-3-2

Abstract

Background: Head and neck carcinomas are the fifth most common cancer worldwide. Squamous cell carcinoma of the head and neck (HNSCC) is a highly heterogeneous tumor. Additional clinical and biological factors are needed to improve tumor diagnosis and to identify subsets of patients with unfavorable outcome. Several recent studies showed that cancer cells stimulate lipid metabolism during tumor progression. Studies have revealed the involvement of fatty acid binding proteins (FABPs) expression in the pathology of different diseases including malignant neoplasms. It has been suggested that the immune changes occurring in the tumour environment determine its aggressive behavior, these changes may affect the prognosis and treatment outcomes in patients with cancer. The tumor necrosis factor (TNF-α) is a proinflammatory cytokine that expressed in HNSCC has a possible role in cancer invasiveness and the risk of metastases. C-reactive protein (C-RP) is an acute-phase protein that increases in acute, chronic inflammations, infections and tissue damages. It has been suggested that C-RP also is elevated in cancers. Objective: The aim of this study was to determine whether the plasma levels of A-FABP are linked to head and neck cancer, inflammatory markers (TNF-α and C-RP) and tumor characteristics. Subjects and Methods: The present study was conducted on 50 healthy individuals and 50 newly diagnosed patients with histologically confirmed HNSCC that accepted to participate. Patients with distant metastases at time of diagnosis, hepatic insufficiency, active autoimmune or coexisting infectious disease were excluded. The study included HNSCC patients with tumours ranged from stage I-IVA (cT1-4a, N0-2, M0). Age, sex, date of diagnosis, tumor site, grade, TNM stage and treatment were recorded. Results: Statistical analysis of the results showed that the mean values of plasma A-FABP, TNF-α and C-RP in HNSCC patients before treatment were significantly higher than that in control group. The plasma levels of the three biomarkers were significantly decreased after treatment than their corresponding values before treatment and plasma C-RP levels became within the normal control values. The risk for head and neck cancer is significantly increased in higher plasma A-FABP group compared with lower levels group. A significant positive correlation was found between plasma A-FABP and both TNF-α and C-RP. There was also a significant correlation observed between plasma A-FABP levels and clinical stage. On the other hand, no correlation was found between plasma levels of TNF-α or C-RP and clinical stage. The three biomarkers were not correlated with other paramters like patient^'s age, sex, BMI or smoking status. Conclusions: The findings in the present study suggested elevated levels of A-FABP, TNF-α and CRP in HNSCC patients before treatment that significantly decreased after treatment. Higher plasma A-FABP is associated with clinical stage and risk of HNSCC.

Keywords:
Adipocyte-fatty acid binding protein tumour necrosis factor-α C-reactive protein head and neck carcinoma

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References:

[1]	Rezende TMB, de Souza FM, Franco OL. Head and neck cancer. Cancer 2010; 116:4914-25.
[2]	Choi S, Myers JN. Molecular pathogenesis of oral squamous cellcarcinoma: implications for therapy. J Dent Res 2008; 87: 14-32.
[3]	Sotiriou CA, Lothaire PB, Dequanter DB, Cardoso FA, Awada AA. Molecular profiling of head and neck tumors.Curr Opin Oncol 2004;16:211-4.
[4]	Cairns RA, Harris IS, Mak TW. Regulation of cancer cellmetabolism. Nat Rev Cancer 2011:11:85-95.
[5]	Ward PS , Thompson CB. Metabolic reprogramming: a cancer hallmark even Warburg did not anticipate. Cancer Cell 2012:21:297-308.
[6]	Haunerland NH. Spener F. Fatty acid-binding proteins: insights from genetic manipulations. Prog Lipid Res 2004;43:328-49.
[7]	Fang LY, Wong TY, Chiang WF, Chen YL. Fatty-acid-binding protein 5 promotes cell proliferation and invasion in oral squamous cell carcinoma. J Oral Pathol Med 2010;39: 342-8.
[8]	Furuhashi M, Hotamisligil GS. Fatty acid-binding proteins: role in metabolic diseases and potential as drug targets. Nat Rev Drug Discov 2008;7:489-503.
[9]	Smathers RL, Petersen DR. The human fatty-acid binding protein family: evolutionary divergences and functions. Hum Genomics 2011;5:170-191.
[10]	Pries R, Thiel A, Brocks C, Wollenberg B. Secretion of tumor-promoting and immune suppresive cytokines by cell lines of head and neck squamous cell carcinoma. In Vivo 2006; 20:45-8.
[11]	Lathers DM, Young MR. Increased aberrance of cytokine expression in plasma of patients with more advanced squamous cell carcinoma of head and neck. Cytokine 2004; 25: 220-8.
[12]	Bellone G, Smirne C, Mauri FA et al. Cytokine expression profile in human pancreatic carcinoma cells and in surgical specimens: implications for survival. Cancer Immunol Immunother 2005;11:1-15.
[13]	Tselepis C, Perry I, Dawson C, Hardy R, Darnton SJ, McConkey C, et al. Tumour necrosis factor-alpha in Barrett's oesophagus: a potential novelmechanism of action. Oncogene 2002;21:6071-81.
[14]	Szlosarek PW, Balkwill FR. Tumour necrosis factor alpha: a potential target for the therapy of solidtumours. Lancet Oncol 2003;4:565-73
[15]	Pries R, Nitsch S, Wollenberg B. Role of cytokines in head and neck squamous cell carcinoma. Expert Rev Anticancer Ther 2006; 6:1195-203.
[16]	Black S, Kushner I, SamolsD. C-reactive protein. J BiolChem 2004; 279: 48487-90.
[17]	Heikkila K, ebrahim S, lawlor Da. A systematic review of theassociation between circulating concentrations of C- reactive protein and cancer. J epidemiol Commun Health 2007;61:824-33.
[18]	Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A. The American Joint Committee on Cancer: the 7th edition of AJCC cancer staging manual and the future of TNM.Ann SurgOncol 2010;17:1471-4.
[19]	Chin D, Boyle GM, Theile DR, Parsons PG,Coman WB. Molecular introduction to head and neck cancer (HNSCC) carcinogenesis. Br J Plast Surg 2004; 57: 595-602.
[20]	Douglas WG, Tracy E, Tan D, Yu J, Hicks WL, Rigual NR, et al. Development of head and neck squamous cell carcinoma is associated with altered cytokine responsiveness. Mol Cancer Res 2004; 2:585-93.
[21]	Lee D, Wada K, TaniguchiY, AL-Shareef H, Masuda T, UsamiY, et al. Expression of fatty acid binding protein 4 is involved in the cell growth of oral squamous cell carcinoma. Oncol Reports 2014; 31:1116-20.
[22]	Ohyama Y, Kawamoto Y, Chiba T, Kikuchi K, Sakashita H, Imai K. Differential expression of fatty acid-binding proteins and pathological implications in the progression of tongue carcinoma. Mol Clin Oncol. 2014;2:19-25.
[23]	Hancke K, Grubeck D, Hauser N, Kreienberg R, Weiss JM. Adipocyte fatty acid-binding protein as a novel prognostic factor in obese breast cancer patients. Breast Cancer Res Treat. 2010;119:367-7.
[24]	Smathers RL and Petersen DR: The human fattyacid binding protein family: evolutionary divergences and functions. Hum Genomics 2011:5: 17091.
[25]	Nieman KM, Kenny HA, Penicka CV, Ladanyi A, Buell-Gutbrod R, Zillhardt MR, et al. Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Nat Med 2011; 17: 1498-503.
[26]	Schroeder F, Petrescu AD, Huang H,Atshaves BP, McIntosh AL, Martin GG, et al. Role of fatty acidbinding proteins and long chain fatty acids in modulating nuclear receptors and gene transcription. Lipids 2008;43:1-17.
[27]	Hashimoto T, Kusakabe T, Sugino T, Fukuda T, Watanabe K, Sato Y, et al. Expression of heart-type fatty acid-binding protein in human gastric carcinoma and its association with tumor aggressiveness, metastasis and poor prognosis. Pathobiology 2004; 71: 267-73.
[28]	Karakas SE, Almario RU, Kim K. Serum fatty acid binding protein4, free fatty acids, and metabolic risk markers. Metabolism 2009;58:1002-7.
[29]	Bonomi M, Patsias A, Posner M, Sikora A. The role of inflammation in head and neck cancer. Adv Exp Med Biol. 2014;816:107-27.
[30]	Peter F, Wittekindt C, Finkensieper M, Kiehntopf M, Guntinas-Lichius O. Prognostic impact of pretherapeutic Laboratory values in head and neck cancer patients. J Cancer Res Clin Oncol 2013;139:171-8.
[31]	Andersson BA, Lewin F, Lundgren J, Nilsson M, Rutqvist LE, LöfgrenS, et al. Plasma tumor necrosis factor‑α and C‑reactive proteinas biomarker for survival in head and neck squamous cellcarcinoma. J Cancer Res Clin Oncol 2014;14:1592-8.
[32]	Brailo V, Vucicevic-Boras V, Lukac J, Biocina-Lukenda, Zilic-Alajbeg I, Milenovic A, et al. Salivary and serum Interleukin 1 beta, interleukin 6 and tumor necrosis factor Alpha in patients with leukoplakia and oral cancer. Med Oral Patol Oral Cir Bucal 2012;17:e10-5.
[33]	Green VL, Michno A, Greenman J, Stafford ND. Effect of treatment on systemic cytokines in head and neck squamous cell carcinoma patients. Results in Immunology 2012; 2:1-6.
[34]	Allin KH, Bojesen SE, Nordestgaard BG. Base line C-reactive protein is associated with incident cancer and survival in patients with cancer. J Clin Oncol 2009;27: 2217-24.
[35]	Chen HH, Chen IH, Liao CT, Wei FC, Lee LY, et al. Preoperative circulating C-reactive protein levels predict pathological aggressiveness in oral squamous cell carcinoma: a retrospective clinical study. Clin Otolaryngol 2011;36: 147-53.
[36]	Baron JA. Epidemiology of non-steroidal anti-inflammatory drugs and cancer. Prog Exp Tumor Res 2003;37: 1-24.
[37]	Oliveira KG,von Zeidler SV, Lamas AZ, dePodesta JR, Sena A, Souza ED, et al. Relationship of inflammatory markers and pain in patients with head and neck cancer prior to anticancer therapy. Braz J Med Biol Res 2014;47:600-4.
[38]	Khandavilli SD, Ceallaigh PO, Lloyd CJ et al. Serum C-reactive protein as a prognostic indicator in patients with oral Squamous cell carcinoma. Oral Oncol 2009;45: 912-4.
[39]	Chen HH, Wang HM, Fan KH, Lin CY, Yen TC, Liao CT, et al. Pretreatment Levels of C-Reactive Protein and Squamous Cell Carcinoma Antigen for Predicting the Aggressiveness of Pharyngolaryngeal Carcinoma. PLoS ONE 2013;8: e55327.