Ferritin: A potential serum marker for lymph node metastasis in head and neck squamous cell carcinoma

Hu,Zhangwei; Wang,Lei; Han,Yong; Li,Fen; Zheng,Anyuan; Xu,Yong; Wang,Fei; Xiao,Bokui; Chen,Chen; Tao,Zezhang

doi:10.3892/ol.2018.9642

Ferritin: A potential serum marker for lymph node metastasis in head and neck squamous cell carcinoma

Authors:
- Zhangwei Hu
- Lei Wang
- Yong Han
- Fen Li
- Anyuan Zheng
- Yong Xu
- Fei Wang
- Bokui Xiao
- Chen Chen
- Zezhang Tao
View Affiliations

Affiliations: Department of Otolaryngology Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China, Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China, Research Institute of Otolaryngology Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
Published online on: October 30, 2018 https://doi.org/10.3892/ol.2018.9642
Pages: 314-322
Copyright: © Hu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer in the world, yet current treatment options are associated with limited success. The aim of the present study was to investigate the expression of ferritin in HNSCC and clarify whether it may serve as a biomarker for predicting HNSCC metastasis. The chemiluminescent immunoassay method was used to investigate the differences in the serum ferritin (SF) levels between patients with and without tumors, and between HNSCC with and without lymph node metastasis. The iron content and expression levels of ferritin were detected to verify the differences between tumor and normal tissues, and between HNSCC without and with lymph node metastasis. Data from the Gene Expression Omnibus (GEO) dataset was used to support the aforementioned results. No statistically significant difference in the SF level was observed between patients with and without tumors. Iron content and expression levels of ferritin heavy chain (FTH) and ferritin light chain (FTL) were higher in tumor tissues compared with normal tissues. The iron content and expression levels of SF, FTH and FTL were increased in HNSCC with metastasis compared with HNSCC without metastasis. The GEO dataset further verified the results and reported that the expression level of FTH was correlated with the prognosis of patients with HNSCC. Ferritin may not be a biomarker for the early diagnosis of HNSCC. However, an association exists between the expression level of ferritin and HNSCC cervical metastasis. SF may be a potential biomarker for predicting cervical lymph node metastasis in patients with HNSCC.

View Figures

View References

1	Busch C, Becker B, Kriegs M, Gatzemeier F, Krüger K, Möckelmann N, Fritz G, Petersen C, Knecht R, Rothkamm K, et al: Similar cisplatin sensitivity of HPV-positive and -negative HNSCC cell lines. Oncotarget. 7:35832–35842. 2016. View Article : Google Scholar : PubMed/NCBI
2	Suarez C, Rodrigo JP, Robbins KT, Paleri V, Silver CE, Rinaldo A, Medina JE, Hamoir M, Sanabria A, Mondin V, et al: Superselective neck dissection: Rationale, indications, and results. Eur Arch Oto-Rhino-L. 270:2815–2821. 2013. View Article : Google Scholar
3	Vigneswaran N and Williams MD: Epidemiologic trends in head and neck cancer and aids in diagnosis. Oral Maxillofac Surg Clin North Am. 26:123–141. 2014. View Article : Google Scholar : PubMed/NCBI
4	Argiris A, Karamouzis MV, Raben D and Ferris RL: Head and neck cancer. Lancet. 371:1695–1709. 2008. View Article : Google Scholar : PubMed/NCBI
5	Trivedi S, Mattos J, Gooding W, Godfrey TE and Ferris RL: Correlation of tumor marker expression with nodal disease burden in metastatic head and neck cancer. Otolaryngol Head Neck Surg. 149:261–268. 2013. View Article : Google Scholar : PubMed/NCBI
6	SV T and FM T: Iron and cancer: More ore to be mined. Nat Rev Cancer. 13:342–355. 2013. View Article : Google Scholar : PubMed/NCBI
7	Lenarduzzi M, Hui AB, Yue S, Ito E, Shi W, Williams J, Bruce J, Sakemura-Nakatsugawa N, Xu W, Schimmer A, et al: Hemochromatosis enhances tumor progression via upregulation of intracellular iron in head and neck cancer. PLoS One. 8:e740752013. View Article : Google Scholar : PubMed/NCBI
8	Ahn SH, Lee S, Kim H, Lee SH, Kim BJ and Koh JM: Higher serum ferritin level and lower femur neck strength in women at the stage of bone loss (≥45 years of age): The fourth Korea national health and nutrition examination survey (Knhanes IV). Endocr Res. 41:334–342. 2016. View Article : Google Scholar : PubMed/NCBI
9	Shi HB, Li XD, Jiang JT, Zhao WQ, Ji M and Wu CP: Serum ferritin is elevated in advanced non-small cell lung cancer patients and is associated with efficacy of platinum-based chemotherapy. J Cancer Res Ther. 10:681–685. 2014.PubMed/NCBI
10	Zhao Y, Wang M, Cui C, Zhang L, Liao F, Li H and Wu X: Significance of combined tests of serum golgi glycoprotein 73 and other biomarkers in diagnosis of small primary hepatocellular carcinoma. Cancer Biomark. 15:677–683. 2015. View Article : Google Scholar : PubMed/NCBI
11	Arenas-Salinas M, Townsend PD, Brito C, Marquez V, Marabolli V, Gonzalez-Nilo F, Matias C, Watt RK, López-Castro JD, Domínguez-Vera J, et al: The crystal structure of ferritin from chlorobium tepidum reveals a new conformation of the 4-fold channel for this protein family. Biochimie. 106:39–47. 2014. View Article : Google Scholar : PubMed/NCBI
12	Memon S, Gao RC, Jiang RZ, Si WN and Zhang XH: Deciphering the evolution of ferritin gene family in various living organisms. Pak J Agr Sci. 52:1055–1063. 2015.
13	Timoshnikov VA, Kobzeva TV, Polyakov NE and Kontoghiorghes GJ: Inhibition of Fe(2+)- and Fe(3+)-induced hydroxyl radical production by the iron-chelating drug deferiprone. Free Radic Biol Med. 78:118–122. 2015. View Article : Google Scholar : PubMed/NCBI
14	Ma X, Wang x, Gao X, Wang L, Lu Y, Gao P, Deng W, Yu P, Ma J, Guo J, et al: Identification of five human novel genes associated with cell proliferation by cell-based screening from an expressed cDNA ORF library. Life Sci. 81:1141–1151. 2007. View Article : Google Scholar : PubMed/NCBI
15	Han LL, Wang YX, Li J, Zhang XL, Bian C, Wang H, Du S and Suo LN: Gender differences in associations of serum ferritin and diabetes, metabolic syndrome, and obesity in the China health and nutrition survey. Mol Nutr Food Res. 58:2189–2195. 2014. View Article : Google Scholar : PubMed/NCBI
16	Kato I, Dnistrian AM, Schwartz M, Toniolo P, Koenig K, Shore RE, Zeleniuch-Jacquotte A, Akhmedkhanov A and Riboli E: Risk of iron overload among middle-aged women. Int J Vitam Nutr Res. 70:119–125. 2000. View Article : Google Scholar : PubMed/NCBI
17	Rychtarcikova Z, Lettlova S, Tomkova V, Korenkova V, Langerova L, Simonova E, Zjablovskaja P, Alberich-Jorda M, Neuzil J and Truksa J: Tumor-initiating cells of breast and prostate origin show alterations in the expression of genes related to iron metabolism. Oncotarget. 8:6376–6398. 2017. View Article : Google Scholar : PubMed/NCBI
18	Pizzamiglio S, Bortoli MD, Taverna E, Signore M, Veneroni S, Cho WC, Orlandi R, Verderio P and Bongarzone I: Expression of iron-related proteins differentiate non-cancerous and dancerous breast tumors. Int J Mol Sci. 18:E4102017. View Article : Google Scholar : PubMed/NCBI
19	Wang X, Peng A, Zeng J, Liu X, Wang B, Fang X, Wang F, Ren G and Min J: Serum ferritin in combination with prostate-specific antigen improves predictive accuracy for prostate cancer. Oncotarget. 8:17862–17872. 2017.PubMed/NCBI
20	Daher R, Manceau H and Karim Z: Iron metabolism and the role of the iron-regulating hormone hepcidin in health and disease. Presse Med. 46:E272–E278. 2017. View Article : Google Scholar : PubMed/NCBI
21	Jablonska E, Socha K, Reszka E, Wieczorek E, Skokowski J, Kalinowski L, Fendler W, Seroczynska B, Wozniak M, Borawska MH, et al: Cadmium, arsenic, selenium and iron-Implications for tumor progression in breast cancer. Environ Toxicol Pharmacol. 53:151–157. 2017. View Article : Google Scholar : PubMed/NCBI
22	Jeong SM, Hwang S and Seong RH: Transferrin receptor regulates pancreatic cancer growth by modulating mitochondrial respiration and ROS generation. Biochem Biophys Res Commun. 471:373–379. 2016. View Article : Google Scholar : PubMed/NCBI
23	Jeong SM, Lee J, Finley LW, Schmidt PJ, Fleming MD and Haigis MC: SIRT3 regulates cellular iron metabolism and cancer growth by repressing iron regulatory protein 1. Oncogene. 34:2115–2124. 2015. View Article : Google Scholar : PubMed/NCBI
24	Guo W, Zhang S, Chen Y, Zhang D, Yuan L, Cong H and Liu S: An important role of the hepcidin-ferroportin signaling in affecting tumor growth and metastasis. Acta Bioch Bioph Sin (Shanghai). 47:703–715. 2015. View Article : Google Scholar
25	Chen Y, Zhang Z, Yang K, Du J, Xu Y and Liu S: Myeloid zinc-finger 1 (MZF-1) suppresses prostate tumor growth through enforcing ferroportin-conducted iron egress. Oncogene. 34:3839–3847. 2015. View Article : Google Scholar : PubMed/NCBI
26	Kell DB and Pretorius E: Serum ferritin is an important inflammatory disease marker, as it is mainly a leakage product from damaged cells. Metallomics. 6:748–773. 2014. View Article : Google Scholar : PubMed/NCBI
27	Gartner A, Berger J, Bour A, El Ati J, Traissac P, Landais E, El Kabbaj S and Delpeuch F: Assessment of iron deficiency in the context of the obesity epidemic: Importance of correcting serum ferritin concentrations for inflammation. Am J Clin Nutr. 98:821–826. 2013. View Article : Google Scholar : PubMed/NCBI
28	Coffman LG, Parsonage D, D'Agostino R, Torti FM and Torti SV: Regulatory effects of ferritin on angiogenesis. Proc Natl Acad Sci USA. 106:570–575. 2009. View Article : Google Scholar : PubMed/NCBI
29	Liu NQ, De Marchi T, Timmermans AM, Beekhof R, Trapman-Jansen AM, Foekens R, Look MP, van Deurzen CH, Span PN, Sweep FC, et al: Ferritin heavy chain in triple negative breast cancer: A favorable prognostic marker that relates to a cluster of differentiation 8 positive (CD⁸⁺) effector T-cell response. Mol Cell Proteomics. 13:1814–1827. 2014. View Article : Google Scholar : PubMed/NCBI
30	Rosager AM, Sorensen MD, Dahlrot RH, Hansen S, Schonberg DL, Rich JN, Lathia JD and Kristensen BW: Transferrin receptor-1 and ferritin heavy and light chains in astrocytic brain tumors: Expression and prognostic value. PloS One. 12:e01829542017. View Article : Google Scholar : PubMed/NCBI
31	Zhukova OS, Smirnova ZS, Chikileva IO and Kiselevskii MV: Antiproliferative activity of a new nitrosyl iron complex with cysteamine in human tumor cells in vitro. Bull Exp Biol Med. 162:583–588. 2017. View Article : Google Scholar : PubMed/NCBI
32	Mahajan UM, Teller S, Sendler M, Palankar R, van den Brandt C, Schwaiger T, Kühn JP, Ribback S, Glöckl G, Evert M, et al: Tumour-specific delivery of siRNA-coupled superparamagnetic iron oxide nanoparticles, targeted against PLK1, stops progression of pancreatic cancer. Gut. 65:1838–1849. 2016. View Article : Google Scholar : PubMed/NCBI
33	Kir D, Saluja M, Modi S, Venkatachalam A, Schnettler E, Roy S and Ramakrishnan S: Cell-permeable iron inhibits vascular endothelial growth factor receptor-2 signaling and tumor angiogenesis. Oncotarget. 7:65348–65363. 2016. View Article : Google Scholar : PubMed/NCBI
34	Zanganeh S, Hutter G, Spitler R, Lenkov O, Mahmoudi M, Shaw A, Pajarinen JS, Nejadnik H, Goodman S, Moseley M, et al: Iron oxide nanoparticles inhibit tumour growth by inducing pro-inflammatory macrophage polarization in tumour tissues. Nat Nanotechnol. 11:986–994. 2016. View Article : Google Scholar : PubMed/NCBI
35	Heusch P, Sproll C, Buchbender C, Rieser E, Terjung J, Antke C, Boeck I, Macht S, Scherer A, Antoch G, et al: Diagnostic accuracy of ultrasound, ¹⁸F-FDG-PET/CT, and fused ¹⁸F-FDG-PET-MR images with DWI for the detection of cervical lymph node metastases of HNSCC. Clin Oral Investig. 18:969–978. 2014. View Article : Google Scholar : PubMed/NCBI