转铁蛋白受体1在头颈肿瘤中的表达及其意义
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摘要
目的:观察转铁蛋白受体1(TFR1)在头颈肿瘤中的表达,并分析其表达水平与患者临床病理特征的关系。方法:通过挖掘cDNA表达谱芯片(GSE33205、GSE29330)和人类肿瘤基因组(TCGA)中头颈肿瘤的数据,比较TFR1在肿瘤组织和正常组织中的转录水平,用KM-plotter在线软件研究TFR1表达与患者总生存率关系,进一步用头颈肿瘤组织芯片免疫组化技术检测TFR1的蛋白表达情况。结果:生物信息分析结果提示,头颈肿瘤中TFR1的表达较正常对照组织明显上调(P<0.05),TFR1高表达患者的总生存率较低(HR=1.43;P=0.0084)。免疫组化结果提示TFR1在肿瘤组织中表达较正常上调(P<0.05),高表达TFR1的头颈肿瘤患者有不良的预后(更易发生转移、更高的T分期,P<0.05)。结论:TFR1在头颈肿瘤中表达上调,可能参与肿瘤的发生和发展。
Objective:To investigate the expression of transferrin receptor 1(TFR1) in head and neck cancer(HNC) and assess the association between the expression level of TFR1 and clinical characteristics of HNC patients.Methods:Bioinformatics microarray(GSE33205 and GSE29330) and the cancer genome atlas(TCGA) were extracted to compare the transcriptional level of TFR1 in HNC tissues and normal tissues.KM-plotter online software was used to explore the relationship between TFR1 expression and overall survival(OS) rate.The protein expression of TFR1 in tumor tissue microarray was detected by immunohistochemistry.Results:Bioinformatic analysis indicated that TFR1 was up-regulated in HNC(P<0.05).Patients with TFR1 over-expression had lower OS rate than those with low-expression of TFR1(HR=1.43,P=0.0084).The TFR1 expression was up-regulated in tumor tissues(P<0.05).Patients with high TFR1 expression had poor prognosis(more likely to metastasize and higher T stage,P<0.05).Conclusion:TFR1 expression was up-regulated in HNC patients that possibly involved in the occurrence and development of HNC.
Objective:To investigate the expression of transferrin receptor 1(TFR1) in head and neck cancer(HNC) and assess the association between the expression level of TFR1 and clinical characteristics of HNC patients.Methods:Bioinformatics microarray(GSE33205 and GSE29330) and the cancer genome atlas(TCGA) were extracted to compare the transcriptional level of TFR1 in HNC tissues and normal tissues.KM-plotter online software was used to explore the relationship between TFR1 expression and overall survival(OS) rate.The protein expression of TFR1 in tumor tissue microarray was detected by immunohistochemistry.Results:Bioinformatic analysis indicated that TFR1 was up-regulated in HNC(P<0.05).Patients with TFR1 over-expression had lower OS rate than those with low-expression of TFR1(HR=1.43,P=0.0084).The TFR1 expression was up-regulated in tumor tissues(P<0.05).Patients with high TFR1 expression had poor prognosis(more likely to metastasize and higher T stage,P<0.05).Conclusion:TFR1 expression was up-regulated in HNC patients that possibly involved in the occurrence and development of HNC.
引文
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[2] CHEN W,ZHENG R,BAADE P D,et al.Cancer statistics in china,2015[J].CA:a Cancer Journal for Clinicians,2016,66(2):115-132.
[3] MARUR S,FORASTIERE A A.Head and neck squamous cell carcinoma:update on epidemiology,diagnosis,and treatment[J].Mayo Clinic Proceedings,2016,91(3):386-396.
[4] TORTI S V,TORTI F M.Iron and cancer:More ore to be mined[J].Nature Reviews Cancer,2013,13(5):342-355.
[5] BYSTROM L M,RⅣELLA S.Cancer cells with irons in the fire[J].Free Radical Biology & Medicine,2015,79(337-342.
[6] MANZ D H,BLANCHETTE N L,PAUL B T,et al.Iron and cancer:Recent insights[J].Annals of the New York Academy of Sciences,2016,1368(1):149-161.
[7] NAI A,LIDONNICI M R,RAUSA M,et al.The second transferrin receptor regulates red blood cell production in mice[J].Blood,2015,125(7):1170-1179.
[8] SHEN Y,LI X,DONG D,et al.Transferrin receptor 1 in cancer:a new sight for cancer therapy[J].American Journal of Cancer Research,2018,8(6):916-931.
[9] DANIELS T R,DELGADO T,RODRIGUEZ J A,et al.The transferrin receptor part i:Biology and targeting with cytotoxic antibodies for the treatment of cancer[J].Clinical Immunology,2006,121(2):144-158.
[10] CAI J,GU B,CAO F,et al.A transferrin-target magnetic/fluorescent dual-mode probe significantly enhances the diagnosis of non-small cell lung cancer[J].Oncotarget,2016,7(26):40047-40059.
[11] JEONG D E,SONG H J,LIM S,et al.Repurposing the anti-malarial drug artesunate as a novel therapeutic agent for metastatic renal cell carcinoma due to its attenuation of tumor growth,metastasis,and angiogenesis[J].Oncotarget,2015,6(32):33046-33064.
[12] HABASHY H O,POWE D G,STAKA C M,et al.Transferrin receptor (cd71) is a marker of poor prognosis in breast cancer and can predict response to tamoxifen[J].Breast Cancer Research and Treatment,2010,119(2):283-293.
[13] SINGH M,MUGLER K,HAILOO D W,et al.Differential expression of transferrin receptor (tfr) in a spectrum of normal to malignant breast tissues:Implications for in situ and invasive carcinoma[J].Applied Immunohistochemistry & Molecular Morphology,2011,19(5):417-423.
[14] TAKAHASHI M,SHIBUTANI M,WOO G H,et al.Cellular distributions of molecules with altered expression specific to the tumor promotion process from the early stage in a rat two-stage hepatocarcinogenesis model[J].Carcinogenesis,2008,29(11):2218-2226.
[15] CHIRASANI S R,MARKOVIC D S,SYNOWITZ M,et al.Transferrin-receptor-mediated iron accumulation controls proliferation and glutamate release in glioma cells[J].Journal of Molecular Medicine,2009,87(2):153-167.
[16] WANG B,ZHANG J,SONG F,et al.EGFR regulates iron homeostasis to promote cancer growth through redistribution of transferrin receptor 1[J].Cancer Letters,2016,381(2):331-340.