转铁蛋白受体1与早期生长反应因子4在宫颈癌组织中的表达及其临床意义
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摘要
为研究转铁蛋白受体1(transferrin receptor type 1,TfR1)与早期生长反应因子4(early growth response protein 4, EGR4)在宫颈癌(uterine cervical carcinoma, UCC)组织中的表达水平,并分析其与UCC临床病理分期的相关性,选取2012年3月至2018年5月于武汉市第四医院就诊的慢性宫颈炎患者33例、宫颈上皮内瘤变(cervical intraepithelial neoplasia, CIN)患者78例、宫颈鳞癌患者63例。采集宫颈炎症和癌变组织,采用免疫组织化学法检测组织中TfR1与EGR4的表达水平,并分析两者之间的相关性及其与宫颈鳞癌临床病理分期的关系。结果显示,TfR1与EGR4在慢性宫颈炎、CIN及宫颈鳞癌组织中均有表达,其中在慢性宫颈炎组织中的表达水平最低(分别为6.1%、9.1%),而在CIN组织中的表达水平随分期的增加而上升,在宫颈鳞癌组织中的表达水平最高(分别为74.6%、57.1%)。相关性分析显示,TfR1与EGR4的表达呈正相关(r_s=0.695,P<0.001),而两者表达水平均与患者年龄、肿瘤大小无关;TfR1的表达水平在不同国际肿瘤学会和国际妇产科协会(the International Federation of Gynecology and Obstetrics, FIGO)分期和分化程度患者中存在差异(χ~2=16.937,P<0.001;χ~2=8.051,P=0.018),EGR4的表达水平则仅在不同FIGO分期患者中不同(χ~2=8.974,P=0.003)。提示在宫颈鳞癌的发生、发展过程中TfR1与EGR4起着重要作用,其中TfR1的表达随着肿瘤细胞分化程度的降低、FIGO分期的增加而上升,EGR4的表达水平则仅随FIGO分期的增加而上升。
To investigate the expressions and clinical significance of transferrin receptor type 1(TfR1) and early growth response protein 4(EGR4) in uterine cervical carcinoma(UCC), and to analyse its correlation with the clinicopathological staging of UCC, expression levels of TfR1 and EGR4 in tissues from 33 patients of chronic cervicitis, 78 patients of cervical intraepithelial neoplasia(CIN) and 63 patients of cervical squamous carcinoma during March 2012 to May 2018 were detected by immunohistochemical method. The correlation between TfR1 and EGR4, as well as their relationship with the clinicopathologic staging of cervical squamous carcinoma were analysed. Both TfR1 and EGR4 were found in chronic cervicitis, CIN and cervical squamous carcinoma tissues. The expressions of TfR1 and EGR4 in chronic cervicitis tissues ranked the lowest with 6.1% and 9.1% respectively. While in CIN tissues, the expressions of the above two biomarkers increased along with the increase of the pathological grade. The expressions of TfR1 and EGR4 in cervical squamous carcinoma tissues presented the highest level(74.6%,57.1% respectively). According to the correlation analysis, the expression of TfR1 was positively related to that of EGR4(r_s = 0.695, P < 0.001). However, the expressions of both were independent of patient age and tumor size. Furthermore, the level of TfR1 was different with the International Federation of Gynecology ond Obstetrics(FIGO) grade and differentiation(χ~2 = 16.937,P < 0.001; χ~2 = 8.051,P=0.018), while EGR4 was only different with FIGO grade(χ~2 = 8.974, P=0.003). TfR1 and EGR4 play important roles in the onset and progression of cervical squamous carcinoma. The expression of TfR1 increases with the decrease of tumor cell differentiation and the improvement of FIGO stage, while the expression of EGR4 only elevates with the increase of FIGO stage.
To investigate the expressions and clinical significance of transferrin receptor type 1(TfR1) and early growth response protein 4(EGR4) in uterine cervical carcinoma(UCC), and to analyse its correlation with the clinicopathological staging of UCC, expression levels of TfR1 and EGR4 in tissues from 33 patients of chronic cervicitis, 78 patients of cervical intraepithelial neoplasia(CIN) and 63 patients of cervical squamous carcinoma during March 2012 to May 2018 were detected by immunohistochemical method. The correlation between TfR1 and EGR4, as well as their relationship with the clinicopathologic staging of cervical squamous carcinoma were analysed. Both TfR1 and EGR4 were found in chronic cervicitis, CIN and cervical squamous carcinoma tissues. The expressions of TfR1 and EGR4 in chronic cervicitis tissues ranked the lowest with 6.1% and 9.1% respectively. While in CIN tissues, the expressions of the above two biomarkers increased along with the increase of the pathological grade. The expressions of TfR1 and EGR4 in cervical squamous carcinoma tissues presented the highest level(74.6%,57.1% respectively). According to the correlation analysis, the expression of TfR1 was positively related to that of EGR4(r_s = 0.695, P < 0.001). However, the expressions of both were independent of patient age and tumor size. Furthermore, the level of TfR1 was different with the International Federation of Gynecology ond Obstetrics(FIGO) grade and differentiation(χ~2 = 16.937,P < 0.001; χ~2 = 8.051,P=0.018), while EGR4 was only different with FIGO grade(χ~2 = 8.974, P=0.003). TfR1 and EGR4 play important roles in the onset and progression of cervical squamous carcinoma. The expression of TfR1 increases with the decrease of tumor cell differentiation and the improvement of FIGO stage, while the expression of EGR4 only elevates with the increase of FIGO stage.
引文
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[12] Buas MF,Rho JH,Chai X,et al.Candidate early detection protein biomarkers for ER+/PR+ invasive ductal breast carcinoma identified using pre-clinical plasma from the WHI observational study[J].Breast Cancer Res Treat,2015,153(2):445-454.
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[16] Decker EL,Nehmann N,Kampen E,et al.Early growth response proteins (EGR) and nuclear factors of activated T cells (NFAT) form heterodimers and regulate proinflammatory cytokine gene expression[J].Nucleic Acids Res,2003,31(3):911-921.
[17] Ma L,Yu Y,Qu,X.Suppressing serum response factor inhibits invasion in cervical cancer cell lines via regulating Egr-1 and epithelial-mesenchymal transition[J].Int J Mol Med,2019,43(1):614-620.
[2] Cancer Genome Atlas Research Network,Albert Einstein College of Medicine,Analytical Biological Services,et al.Integrated genomic and molecular characterization of cervical cancer[J].Nature,2017,543(7645):378-384.
[3] Liu P,Iden M,Fye S,et al.Targeted,deep sequencing reveals full methylation profiles of multiple HPV types and potential biomarkers for cervical cancer progression[J].Cancer Epidemiol Biomarkers Prev,2017,26(4):642-650.
[4] Dong D,Zhang G,Yang J,et al.The role of iron metabolism in cancer therapy focusing on tumor-associated macrophages[J].J Cell Physiol,2019,234(6):8028-8039.
[5] Matsuo T,Dat le T,Komatsu M,et al.Early growth response 4 is involved in cell proliferation of small cell lung cancer through transcriptional activation of its downstream genes[J].PLoS One,2014,9(11):e113606.
[6] 周琦,吴小华,刘继红,等.宫颈癌诊断与治疗指南(第四版)[J].中国实用妇科与产科杂志,2018,34(6):613-622.
[7] 陈春林.中国宫颈癌临床诊疗与大数据[J].中国实用妇科与产科杂志,2018,34(1):25-29.
[8] Torre LA,Siegel RL,Ward EM,et al.Global cancer incidence and mortality rates and trends—an update[J].Cancer Epidemiol Biomarkers Prev,2016,25(1):16-27.
[9] Jhaveri A,Deshpande P,Pattni B,et al.Transferrin-targeted,resveratrol-loaded liposomes for the treatment of glioblastoma[J].J Control Release,2018,277:89-101.
[10] Papanikolaou G,Pantopoulos K.Systemic iron homeostasis and erythropoiesis[J].IUBMB Life,2017,69(6):399-413.
[11] Jeong SM,Hwang S,Seong RH.Transferrin receptor regulates pancreatic cancer growth by modulating mitochondrial respiration and ROS generation[J].Biochem Biophys Res Commun,2016,471(3):373-379.
[12] Buas MF,Rho JH,Chai X,et al.Candidate early detection protein biomarkers for ER+/PR+ invasive ductal breast carcinoma identified using pre-clinical plasma from the WHI observational study[J].Breast Cancer Res Treat,2015,153(2):445-454.
[13] Rychtarcikova Z,Lettlova S,Tomkova V,et al.Tumor-initiating cells of breast and prostate origin show alterations in the expression of genes related to iron metabolism[J].Oncotarget,2017,8(4):6376-6398.
[14] Kindrat I,Tryndyak V,de Conti A,et al.MicroRNA-152-mediated dysregulation of hepatic transferrin receptor 1 in liver carcinogenesis[J].Oncotarget,2016,7(2):1276-1287.
[15] Chan KT,Choi MY,Lai KY,et al.Overexpression of trans-ferrin receptor CD71 and its tumorigenic properties in esophageal squamous cell carcinoma[J].Oncol Rep,2014,31(3):1296-1304.
[16] Decker EL,Nehmann N,Kampen E,et al.Early growth response proteins (EGR) and nuclear factors of activated T cells (NFAT) form heterodimers and regulate proinflammatory cytokine gene expression[J].Nucleic Acids Res,2003,31(3):911-921.
[17] Ma L,Yu Y,Qu,X.Suppressing serum response factor inhibits invasion in cervical cancer cell lines via regulating Egr-1 and epithelial-mesenchymal transition[J].Int J Mol Med,2019,43(1):614-620.