白介素10、E26转录因子1和肿瘤相关巨噬细胞在宫颈癌中的表达研究

doi:10.3969/j.issn.1007-9572.2016.27.010

摘要/Abstract

摘要： 背景　宫颈癌是女性高发的恶性肿瘤之一。白介素10（IL-10）作为一种具有免疫抑制作用的细胞因子对宫颈癌变的发生、发展具有重要作用。肿瘤相关巨噬细胞（TAM）、E26转录因子1（Ets1）均可促进肿瘤的生长、侵袭和迁移。目的　探讨宫颈癌组织中IL-10、Ets1和TAM的表达情况及其与宫颈癌的关系。方法　选取2014年9月—2016年3月唐山工人医院住院部收治的宫颈上皮内瘤变（CIN）患者72例为CIN组，宫颈鳞癌患者76例为鳞状细胞癌（SCC）组，行全子宫切除术的子宫良性病变患者40例为正常组。采用简单随机抽样法选取3例SCC组宫颈组织及3例正常组宫颈组织进行基因芯片杂交测序；采用RT-qPCR法检测所有患者宫颈组织中IL-10、Ets1 mRNA表达水平，免疫双荧光共定位法检测宫颈组织中TAM情况及表达IL-10、Ets1的TAM（IL-10+ TAM、Ets1+ TAM）水平，分析IL-10+ TAM、Ets1+ TAM水平与SCC组患者临床资料的关系。结果　与正常组宫颈组织比较，IL-10在SCC组宫颈组织中表达上调3.4倍，Ets1表达上调2.9倍（P0.05）；SCC组患者IL-10+ TAM、Ets1+ TAM水平与分化程度、临床分期、淋巴结转移有关（P<0.05）。结论　IL-10、Ets1和TAM表达水平随宫颈病变进展而升高，TAM及其分泌的IL-10、Ets1可能与宫颈癌及临床预后有关。

关键词: 宫颈肿瘤, 白细胞介素10, E26转录因子1, 巨噬细胞

Abstract: Background　Cervical cancer is one of the women malignant tumors with high incidence.Interleukin 10 （IL-10）,as a kind of cytokine with immunosuppressive effects,plays an important role in the occurrence and development of cervical cancer.Both tumor-associated macrophages （TAM） and E26 transcription factor 1 （Ets1） can promote tumor growth,invasion and migration.Objective　To investigate the expression of IL-10,Ets1 and TAM in cervical carcinoma tissues and their correlation with cervical cancer.Methods　72 cervical intraepithelial neoplasia （CIN） patients,76 cervical squamous cell carcinoma （SCC） patients and 40 benign uterine lesion patients underwent total hysterectomy,who were under treatment in Inpatient Department of Tangshan Gongren Hospital from September 2014 to March 2016,were selected into CIN group,SCC group and normal group separately.3 subjects with cervical tissues in SCC group and 3 with cervical tissues in normal group were selected to make microarray hybridization sequencing by simple random sampling method;the expression levels of IL-10 and Ets1 mRNA in cervical tissues were detected by RT-qPCR method in all patients,the status and expression of TAM and TAM that IL-10 and Ets1 levels expressed by TAM （IL-10+ TAM,Ets1+ TAM） were detected by double immunofluorescence colocalization method,and the relationship between levels of IL-10+ TAM,Ets1+ TAM and clinical data was analyzed.Results　Comparing with cervical tissues of normal group,the expression of IL-10 in cervical tissues of SCC group upregulated 3.4 times,and Ets1 upregulated 2.9 times （P<0.05）.Expression levels of IL-10 and Ets1 mRNA in CIN group and SCC group were higher than those in normal group （P<0.05）;expression levels of IL-10 and Ets1 mRNA in SCC group were higher than those in CIN group （P<0.05）.The expression level of IL-10 mRNA in CIN group and SCC group was positively correlated with the expression level of Ets1 mRNA （r=0.453,P<0.01;r=0.456,P<0.01）.TAM increased gradually in cervical tissues in normal group,CIN group and SCC group.The levels of IL-10+ TAM and Ets1+ TAM in CIN group and SCC group were higher than those in normal group （P<0.05）;the levels of IL-10+ TAM and Ets1+ TAM in SCC group were higher than those in CIN group （P<0.05）.The levels of IL-10+ TAM and Ets1+ TAM in patients of SCC group were not related to age and tumor size （P>0.05）;the levels of IL-10+ TAM and Ets1+ TAM in patients of SCC group were related to differentiated degree,clinical stage of cervical cancer and lymph node metastasis （P<0.05）.Conclusion　The expression level of IL-10,Ets1 and TAM increases with the progression of cervical lesions,TAM and its secreted IL-10 and Ets1 may be related to cervical cancer and clinical prognosis.

Key words: Uterine cervical neoplasms, Interleukin-10, Ets1 transcription factor, Macrophages

张琪, 马冬, 常凌雅, 张丽杰, 闫錫钊, 王洋, 陈丽蓉, 李鸥. 白介素10、E26转录因子1和肿瘤相关巨噬细胞在宫颈癌中的表达研究[J]. 中国全科医学, 2016, 19(27): 3306-3310.

ZHANG Qi, MA Dong, CHANG Ling-ya, ZHANG Li-jie, YAN Xi-zhao, WANG Yang, CHEN Li-rong, LI Ou. Expression of Interleukin-10,E26 Transformation Factor-1 and Tumor-associated Macrophages in Cervical Cancer[J]. Chinese General Practice, 2016, 19(27): 3306-3310.

参考文献

［1］杨艳艳,马冬,刘桂艳,等.细胞因子DNA甲基化导致免疫失衡与宫颈癌关系的研究进展［J］.中国妇幼保健,2014,29（5）:812-814. ［2］HEDRICH C M,BREAM J H.Cell type-specific regulation of IL-10 expression in inflammation and disease［J］.Immunol Res,2010,47（1/2/3）:185-206. ［3］YORDY J S,LI R,SEMENTCHENKO V I,et al.SP100 expression modulates ETS1 transcriptional activity and inhibits cell invasion［J］.Oncogene,2004,23（39）:6654-6665. ［4］WATANABE D,TAKAGI H,SUZUMA K,et al.Transcription factor Ets-1 mediates ischemia- and vascular endothelial growth factor-dependent retinal neovascularization［J］.Am J Pathol,2004,164（5）:1827-1835. ［5］POLLARD J W.Tumour-educated macrophages promote tumor progression and metastasis［J］.Nat Rev Cancer,2004,4（1）:71-78. ［6］李妍,郝权.高迁移率族蛋白1和肿瘤相关巨噬细胞与宫颈癌淋巴管密度的相关性研究［J］.中国肿瘤临床,2014,41（4）:222-226. LI Y,HAO Q.Correlation of lymphatic vessel density with a high mobility group Box-1 protein and tumor-associated macrophages in cervical carcinoma［J］.Chinese Journal of Clinical Oncology,2014,41（4）:222-226. ［7］DING H,CAI J,MAO M,et al.Tumor-associated macrophages induce lymphangiogenesis in cervical cancer via interaction with tumor cells［J］.APMIS,2014,122（11）:1059-1069. ［8］JI R C.Macrophages are important mediators of either tumor- or inflammation-induced lymphangesis［J］.Cell Mol Life Sci,2012,69（6）:897-914. ［9］TANG X.Tumor-associated macrophages as potential diagnostic and prognostic biomarkers in breast cancer［J］.Cancer Lett,2013,332（1）:3-10. ［10］KIM S,CHO S W,MIN H S,et al.The expression of tumor-associated macrophages in papillary thyroid carcinoma［J］.Endocrinol Metab,2013,28（3）:192-198. ［11］MUMM J B,EMMERICH J,ZHANG X,et al.IL-10 elicits IFNy-dependent tumor immune surveillance［J］.Cancer Cell,2011,20（6）:781-796. ［12］王艳,李鸥,白娣斯,等.白介素-10基因的表观遗传与宫颈癌研究进展［J］.中国妇幼保健,2012,27（3）:462-464. ［13］ROTHHAMMER T,HAHNE J C,FLORIN A,et al.The Ets-1 transcription factor is involved in the development and invasion of malignant melanoma［J］.Cell Mol Life Sci,2004,61（1）:118-128. ［14］HAMIDULLAH,CHANGKIJA B,KONWAR R.Role of interleukin-10 in breast cancer［J］.Breast Cancer Res Treat,2012,133（1）:11-21. ［15］王晓燕,邵淑丽,赵虹,等.ETS1与宫颈癌发生发展的相关性研究［J］.中国药物与临床,2009,9（7）:582-585. WANG X Y,SHAO S L,ZHAO H,et al.The role of ETS1 in development and progression of cervical cancer［J］.Chinese Remedies & Clinics,2009,9（7）:582-585.

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