Nrf2、HO-1在经典型霍奇金淋巴瘤的表达与其临床特征的关系
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摘要
目的探讨核因子E2相关因子(nuclear factor erythroid-2 related factor 2,Nrf2)和血红素加氧酶-1(hemeoxygenase-1,HO-1)在经典型霍奇金淋巴瘤(classical Hodgkin′s lymphoma,cHL)中的表达及临床意义。方法采用免疫组化SP法检测42例cHL组织(cHL组)及23例淋巴结反应性增生组织(对照组)中Nrf2和HO-1蛋白的表达,并分析两者表达与患者临床病理特征之间的关系。结果 Nrf2和HO-1在cHL组织的阳性率分别为42.9%和47.6%,显著高于淋巴结反应增生组织13.0%和17.4%,两组比较差异有统计学意义(P<0.05)。Nrf2和HO-1表达水平均与cHL患者临床分期、B症状有关(P<0.05),而与患者性别、年龄、病理分型、LDH无关(P>0.05)。Nrf2和HO-1在cHL组织中的表达呈正相关(r=0.619,P<0.05)。结论 Nrf2和HO-1在cHL组织中均呈高表达,其可能在cHL的发生、发展中起重要作用。
Objective To investigate the expression and clinical significance of nuclear factor erythroid-2 related factor 2(Nrf2) and hemeoxygenase-1(HO-1) in classical Hodgkin′s lymphoma(cHL). Methods Expression of Nrf2 and HO-1 protein in 42 cases of cHL tissue and 23 cases of lymph node reactive hyperplasia were detected by immunohistochemical SP method.The relationship between the expression of Nrf2 and HO-1 protein and clinicopathological features of patients was analyzed. Results The positive rates of Nrf2 and HO-1 were significantly higher in cHL tissues(42.9% and 47.6%) than in lymph node hyperplasia tissues(13.0% and 17.4%)(P<0.05). The expressions of Nrf2 and HO-1 were related to Ann Arbor clinical stage and B symptoms, while they were not related to gender, age, pathological type and LDH of cHL patients.There was a positive correlation between the expression of Nrf2 and HO-1 in cHL tissues(r=0.619, P<0.05). Conclusion The expression of Nrf2 and HO-1 are elevated in cHL tissues,which may play an important role in the occurrence and development of cHL.
Objective To investigate the expression and clinical significance of nuclear factor erythroid-2 related factor 2(Nrf2) and hemeoxygenase-1(HO-1) in classical Hodgkin′s lymphoma(cHL). Methods Expression of Nrf2 and HO-1 protein in 42 cases of cHL tissue and 23 cases of lymph node reactive hyperplasia were detected by immunohistochemical SP method.The relationship between the expression of Nrf2 and HO-1 protein and clinicopathological features of patients was analyzed. Results The positive rates of Nrf2 and HO-1 were significantly higher in cHL tissues(42.9% and 47.6%) than in lymph node hyperplasia tissues(13.0% and 17.4%)(P<0.05). The expressions of Nrf2 and HO-1 were related to Ann Arbor clinical stage and B symptoms, while they were not related to gender, age, pathological type and LDH of cHL patients.There was a positive correlation between the expression of Nrf2 and HO-1 in cHL tissues(r=0.619, P<0.05). Conclusion The expression of Nrf2 and HO-1 are elevated in cHL tissues,which may play an important role in the occurrence and development of cHL.
引文
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2 Jona A,Irsai G,Barna S,et al.Rapidly progressing refractory hodgkin lymphoma:a case report and a possible explanation[J].Case Rep Med,2016,2016:7698624
3 Quddus F,Armitage JO.Salvage therapy for Hodgkin′s lymphoma[J].Cancer J,2009,15(2):161-163
4 Paschos A,Pandya R,Duivenvoorden WC,et al.Oxidative stress in prostate cancer:changing research concepts towards a novel paradigm for prevention and therapeutics[J].Prostate Cancer Prostatic Dis,2013,16(3):217-225
5 Sykiotis GP,Habeos IG,Samuelson AV,et al.The role of the antioxidant and longevity-promoting Nrf2 pathway in metabolic regulation[J].Curr Opin Clin Nutr Metab Care,2011,14(1):41-48
6 Jaramillo MC,Zhang DD.The emerging role of the Nrf2-Keap1 signaling pathway in cancer[J].Genes Dev,2013,27(20):2179-2191
7 Jozkowicz A,Was H,Dulak J.Heme oxygenase-1 in tumors:is it a false friend?[J].Antioxid Redox Signal,2007,9(12):2099-2117
8 Na HK,Surh YJ.Oncogenic potential of Nrf2 and its principal target protein heme oxygenase-1[J].Free Radic Biol Med,2014,67:353-365
9 Furfaro AL,Piras S,Domenicotti C,et al.Role of Nrf2,HO-1 and GSH in neuroblastoma cell resistance to bortezomib[J].PLoS One,2016,11(3):e0152465
10 Wang XJ,Sun Z,Villeneuve NF,et al.Nrf2 enhances resistance of cancer cells to chemotherapeutic drugs,the dark side of Nrf2[J].Carcinogenesis,2008,29(6):1235-1243
11 Kawasaki Y,Ishigami S,Arigami T,et al.Clinicopathological significance of nuclear factor (erythroid-2)-related factor 2 (Nrf2) expression in gastric cancer[J].BMC Cancer,2015,15:5
12 Liew PL,Hsu CS,Liu WM,et al.Prognostic and predictive values of Nrf2,Keap1,p16 and E-cadherin expression in ovarian epithelial carcinoma[J].Int J Clin Exp Pathol,2015,8(5):5642-5649
13 Soini Y,Eskelinen M,Juvonen P,et al.Nuclear Nrf2 expression is related to a poor survival in pancreatic adenocarcinoma[J].Pathol Res Pract,2014,210(1):35-39
14 Hjortso MD,Andersen MH.The expression,function and targeting of haem oxygenase-1 in cancer[J].Curr Cancer Drug Targets,2014,14(4):337-347
15 Chau LY.Heme oxygenase-1:emerging target of cancer therapy[J].J Biomed Sci,2015,22:22
16 Furfaro AL,Traverso N,Domenicotti C,et al.The Nrf2/HO-1 axis in cancer cell growth and chemoresistance[J].Oxid Med Cell Longev,2016,2016:1958174
17 Tsai JR,Wang HM,Liu PL,et al.High expression of heme oxygenase-1 is associated with tumor invasiveness and poor clinical outcome in non-small cell lung cancer patients[J].Cell Oncol (Dordr),2012,35(6):461-471
18 Noh SJ,Bae JS,Jamiyandorj U,et al.Expression of nerve growth factor and heme oxygenase-1 predict poor survival of breast carcinoma patients[J].BMC Cancer,2013,13:516
19 Huang J,Guo P,Ma D,et al.Overexpression of heme oxygenase-1 induced by constitutively activated NF-kappaB as a potential therapeutic target for activated B-cell-like diffuse large B-cell lymphoma[J].Int J Oncol,2016,49(1):253-264
20 Mayerhofer M,Gleixner KV,Mayerhofer J,et al.Targeting of heat shock protein 32 (Hsp32)/heme oxygenase-1 (HO-1) in leukemic cells in chronic myeloid leukemia:a novel approach to overcome resistance against imatinib[J].Blood,2008,111(4):2200-2210
21 Cerny-Reiterer S,Meyer RA,Herrmann H,et al.Identification of heat shock protein 32 (Hsp32) as a novel target in acute lymphoblastic leukemia[J].Oncotarget,2014,5(5):1198-1211