宫颈癌组织中Bregs、IL-10及TGF-β表达的相关性及其临床意义
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摘要
目的探讨宫颈癌组织中调节性B细胞(regulatory B cells,Bregs)、白介素-10(interleukin-10,IL-10)、转化生长因子-β(transforming growth factor-β,TGF-β)的表达及其临床意义。方法将2018年1月至2018年12月陆军军医大学第二附属医院收治的102例宫颈癌患者纳入宫颈癌组,并将同期于该院诊治的88例宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)患者纳入CIN组。比较两组患者病变组织中Bregs亚群(Br1和Br3细胞)分布及外周血IL-10、TGF-β的表达水平。采用Pearson相关分析探讨宫颈癌组织中Bregs亚群分布与外周血IL-10、TGF-β表达水平之间的相关性。结果宫颈癌组患者病变组织中Br1细胞和Br3细胞占比及外周血IL-10、TGF-β表达水平均显著高于CIN组(P_均<0.05)。宫颈癌组中国际妇产科联盟(International Federation of Gynecology and Obstetrics,FIGO)分期为Ⅲ期、有淋巴结转移、低分化、深间质浸润患者病变组织中Br1细胞占比及外周血IL-10表达水平均显著高于FIGO分期Ⅱ期和Ⅰ期、无淋巴结转移、高分化、中分化及无深间质浸润者(P_均<0.05),且FIGO分期Ⅱ期、中分化患者病变组织中Br1细胞占比及外周血IL-10表达水平均显著高于FIGO分期Ⅰ期、高分化者(P_均<0.05)。宫颈癌组中FIGO分期Ⅰ期、高分化、无深间质浸润患者组织中Br3细胞占比及外周血TGF-β表达水平均显著低于FIGO分期Ⅲ期、中分化、低分化、深间质浸润者(P_均<0.05)。Pearson相关分析表明:宫颈癌组织中Br1细胞占比与外周血IL-10表达水平呈显著正相关(r=0.501,P <0.05),宫颈癌组织中Br3细胞占比与外周血TGF-β表达水平呈显著正相关(r=0.356,P <0.05)。结论宫颈癌组织中Bregs占比显著升高,其可能参与了宫颈癌的发生发展,并与IL-10、TGF-β的分泌有关。
Objective To investigate the expression and clinical significance of regulatory B cells(Bregs), interleukin-10(IL-10) and transforming growth factor-β(TGF-β) in cervical carcinoma tissue. Method 102 patients with cervical carcinoma treated in the Second Aliated Hospital of the Army Military Medical University from January 2018 to December 2018 were included in cervical carcinoma group, and 88 patients with cervical intraepithelial neoplasia(CIN) in that hospital at the same time were included in CIN group, the distribution of Bregs subsets(Br1 and Br3 cells) and the expression levels of IL-10 and TGF-β in peripheral blood were compared between the two groups. The relationship between the distribution of Bregs subsets and the expression levels of IL-10 and TGF-β in peripheral blood of cervical carcinoma by pearson correlation analysis were analyzed. Result The proportion of Br1 cells and Br3 cells and the expression levels of IL-10 and TGF-β in peripheral blood of patients with cervical carcinoma gruop were signi?cantly higher than those in CIN group(P_(all)< 0.05). The proportion of Br1 cells and the expression level of IL-10 in peripheral blood of patients with International Federation of Gynecology and Obstetrics(FIGO) stageⅢ, lymph node metastasis, poorly differentiation and deep interstitial in?ltration in cervical carcinoma group were signi?cantly higher than those of patients with FIGO stage Ⅱ and Ⅰ, without lymph node metastasis, well differentiation, moderate differentiation and without deep interstitial in?ltration(P_(all)< 0.05), the proportion of Br1 cells and the expression level of IL-10 in peripheral blood of patients with FIGO stageⅡ and moderately differentiated were signi?cantly higher than those of patients with FIGO stage Ⅰ and well differentiated(P_(all)< 0.05). The proportion of Br3 cells and the expression of TGF-β in peripheral blood of patients with FIGO stage Ⅰ, well differentiation and without deep interstitial in?ltration in cervical cancer group were signi?cantly lower than those in FIGO stage Ⅲ, moderately differ entiated,poorly differentiation and deep interstitial in?ltration(P_(all)< 0.05). Pearson correlation analysis showed that the proportion of Br1 cells in cervical carcinoma tissues was positively correlated with the expression level of IL-10 in peripheral blood(r=0.501, P<0.05).The proportion of Br3 cells in cervical carcinoma was positively correlated with the expression of TGF-β in peripheral blood(r=0.356,P < 0.05). Conclusion The proportion of Bregs in cervical carcinoma tissues increased signi?cantly, which may be involved in the occurrence and development of cervical carcinoma, and related to the secretion of IL-10 and TGF-β.
Objective To investigate the expression and clinical significance of regulatory B cells(Bregs), interleukin-10(IL-10) and transforming growth factor-β(TGF-β) in cervical carcinoma tissue. Method 102 patients with cervical carcinoma treated in the Second Aliated Hospital of the Army Military Medical University from January 2018 to December 2018 were included in cervical carcinoma group, and 88 patients with cervical intraepithelial neoplasia(CIN) in that hospital at the same time were included in CIN group, the distribution of Bregs subsets(Br1 and Br3 cells) and the expression levels of IL-10 and TGF-β in peripheral blood were compared between the two groups. The relationship between the distribution of Bregs subsets and the expression levels of IL-10 and TGF-β in peripheral blood of cervical carcinoma by pearson correlation analysis were analyzed. Result The proportion of Br1 cells and Br3 cells and the expression levels of IL-10 and TGF-β in peripheral blood of patients with cervical carcinoma gruop were signi?cantly higher than those in CIN group(P_(all)< 0.05). The proportion of Br1 cells and the expression level of IL-10 in peripheral blood of patients with International Federation of Gynecology and Obstetrics(FIGO) stageⅢ, lymph node metastasis, poorly differentiation and deep interstitial in?ltration in cervical carcinoma group were signi?cantly higher than those of patients with FIGO stage Ⅱ and Ⅰ, without lymph node metastasis, well differentiation, moderate differentiation and without deep interstitial in?ltration(P_(all)< 0.05), the proportion of Br1 cells and the expression level of IL-10 in peripheral blood of patients with FIGO stageⅡ and moderately differentiated were signi?cantly higher than those of patients with FIGO stage Ⅰ and well differentiated(P_(all)< 0.05). The proportion of Br3 cells and the expression of TGF-β in peripheral blood of patients with FIGO stage Ⅰ, well differentiation and without deep interstitial in?ltration in cervical cancer group were signi?cantly lower than those in FIGO stage Ⅲ, moderately differ entiated,poorly differentiation and deep interstitial in?ltration(P_(all)< 0.05). Pearson correlation analysis showed that the proportion of Br1 cells in cervical carcinoma tissues was positively correlated with the expression level of IL-10 in peripheral blood(r=0.501, P<0.05).The proportion of Br3 cells in cervical carcinoma was positively correlated with the expression of TGF-β in peripheral blood(r=0.356,P < 0.05). Conclusion The proportion of Bregs in cervical carcinoma tissues increased signi?cantly, which may be involved in the occurrence and development of cervical carcinoma, and related to the secretion of IL-10 and TGF-β.
引文
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[14]杨绍臻,杜国盛.调节性B细胞与肿瘤免疫[J].癌症进展,2016,14(4):296-299.
[15]Chen T,Song D,Min Z,et al.Perioperative dynamic alterations in peripheral regulatory T and B cells in patients with hepatocellular carcinoma[J].J Transl Med,2012,10:14.
[16]欧洁,吴红艳.调节性B细胞对肿瘤发展促进作用的研究进展[J].基础医学与临床,2019,39(1):110-114.
[17]郑筱男,唐恋莎,韩鑫,等.调节性B细胞抑制肿瘤免疫的研究进展[J].现代预防医学,2018,45(4):761-764.
[18]陈葆国,梅丽萍,郑瑞,等.肺癌患者外周血调节性B细胞的表达及其临床意义[J].解放军医学杂志,2015,40(5):396-399.
[19]孙会,王丙娟,孙慧霞.宫颈癌患者外周血调节性B细胞数量及血清IL-10、TGF-β表达水平[J].中国老年学杂志,2018,38(22):5441-5443.
[20]高峻.宫颈癌患者外周血调节性B细胞亚群的检测及临床意义[J].中国社区医师(医学专业),2011,13(16):227-228.
[21]Lee JH,Noh J,Noh G,et al.Allergen-specific transforming growth factor-β-producing CD19+CD5+regulatory B-cell(Br3)responses in human late eczematous allergic reactions to cow's milk[J].J Interferon Cytokine Res,2011,31(5):441-449.
[22]邢陈,黎燕,沈倍奋,等.调节性B细胞的研究进展[J].国际药学研究杂志,2015,42(3):326-330,354.
[2]Olkhanud PB,Damdinsuren B,Bodogai M,et al.Tumor-evoked regulatory B cells promote breast cancer metastasis by converting resting CD4+T cells to T-regulatory cells[J].Cancer Res,2011,71(10):3505-3515.
[3]廖玲,黄恒柳,章明徐,等.HBV相关性肝癌患者CD19+CD24+CD38+调节性B细胞和IL-10的检测及临床价值[J].第三军医大学学报,2018,40(7):625-630.
[4]石家振,李世宝,周彦.食管癌患者外周血中调节性B细胞检测的临床意义[J].南京医科大学学报(自然科学版),2013,33(2):210-212.
[5]丁婷婷.肺癌中调节性B细胞对免疫的抑制作用及其机制[D].天津:天津医科大学,2016.
[6]Ye ZP,He HY,Wang H,et al.Glioma-derived ADAM10 induces regulatory B cells to suppress CD8+T cells[J].PLoS One,2014,9(8):e105350.
[7]Moreau A,Blair PA,Chai JG,et al.Transitional-2 B cells acquire regulatory function during tolerance induction and contribute to allograft survival[J].Eur J Immunol,2015,45(3):843-853.
[8]Mizoguchi A,Mizoguchi E,Smith RN,et al.Suppressive role of B cells in chronic colitis of T cell receptor alpha mutant mice[J].J Exp Med,1997,186(10):1749-1756.
[9]Noh G,Lee JH.Regulatory B cells and allergic diseases[J].Allergy Asthma Immunol Res,2011,3(3):168-177.
[10]滕士阶,卞光荣,王彦,等.食管癌患者围手术期外周血调节性B细胞的检测及临床意义[J].临床检验杂志,2015,33(10):766-768.
[11]马锡慧,肖漓.淋巴细胞亚群成员研究进展[J].中华细胞与干细胞杂志(电子版),2017,7(3):168-172.
[12]Shi J,Li S,Zhou Y,et al.Perioperative changes in peripheral regulatory B cells of patients with esophageal cancer[J].Mol Med Rep,2014,10(3):1525-1530.
[13]Gong Y,Zhao C,Zhao P.Role of IL-10-producing regulatory B cells in chronic hepatitis B virus infection[J].Dig Dis Sci,2015,60(5):1308-1314.
[14]杨绍臻,杜国盛.调节性B细胞与肿瘤免疫[J].癌症进展,2016,14(4):296-299.
[15]Chen T,Song D,Min Z,et al.Perioperative dynamic alterations in peripheral regulatory T and B cells in patients with hepatocellular carcinoma[J].J Transl Med,2012,10:14.
[16]欧洁,吴红艳.调节性B细胞对肿瘤发展促进作用的研究进展[J].基础医学与临床,2019,39(1):110-114.
[17]郑筱男,唐恋莎,韩鑫,等.调节性B细胞抑制肿瘤免疫的研究进展[J].现代预防医学,2018,45(4):761-764.
[18]陈葆国,梅丽萍,郑瑞,等.肺癌患者外周血调节性B细胞的表达及其临床意义[J].解放军医学杂志,2015,40(5):396-399.
[19]孙会,王丙娟,孙慧霞.宫颈癌患者外周血调节性B细胞数量及血清IL-10、TGF-β表达水平[J].中国老年学杂志,2018,38(22):5441-5443.
[20]高峻.宫颈癌患者外周血调节性B细胞亚群的检测及临床意义[J].中国社区医师(医学专业),2011,13(16):227-228.
[21]Lee JH,Noh J,Noh G,et al.Allergen-specific transforming growth factor-β-producing CD19+CD5+regulatory B-cell(Br3)responses in human late eczematous allergic reactions to cow's milk[J].J Interferon Cytokine Res,2011,31(5):441-449.
[22]邢陈,黎燕,沈倍奋,等.调节性B细胞的研究进展[J].国际药学研究杂志,2015,42(3):326-330,354.