HPV阳性与阴性宫颈病变患者外周血中Foxp3 mRNA及RORγt mRNA的表达
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摘要
目的:观察叉头状转录因子信使核糖核酸(Foxp3 mRNA)、视黄酸相关孤儿受体γt信使核糖核酸(RORγt mRNA)在HPV感染的宫颈病变患者外周血中相对表达量的变化,探讨其与该病变的关系。方法:收集2016-01—2017-06本院门诊及住院宫颈病变患者373例,用聚合酶链式反应(PCR)和基因芯片检测技术筛选出HPV阳性感染者158例,包括宫颈炎组40例、宫颈上皮内瘤变(CIN)76例(CINⅠ级组25例、CINⅡ级组25例、CINⅢ级组26例)、宫颈癌组42例;HPV阴性者215例,包括宫颈炎组124例、CIN 68例(CINⅠ级组26例、CINⅡ级组22例、CINⅢ级组20例)、宫颈癌组23例。选择同期体检健康者为正常对照组(39例)。采用实时荧光定量PCR方法检测受试者外周血单个核细胞中Foxp3mRNA、RORγt mRNA的相对表达量。比较HPV阳性与HPV阴性各组Foxp3mRNA、RORγt mRNA表达差异,分析Foxp3mRNA、RORγt mRNA与宫颈变变严重程度的相关性。结果:随着宫颈病变的加重,HPV阳性检出率增加。HPV阳性各组宫颈病变患者Foxp3mRNA、RORγt mRNA相对表达量的差异均有统计学意义(P<0.05)。Foxp3mRNA相对表达量在宫颈炎组与CINI级组组间差异无统计学意义(P>0.05),其余组间呈CIN I级组0.05),其余组间呈CIN I级组>CINⅡ级组>CINⅢ级组>宫颈癌组,差异有统计学意义(P<0.05)。Foxp3mRNA、RORγt mRNA相对表达量在HPV阴性各组宫颈病变中差异均无统计学意义(P>0.05)。HPV阳性宫颈病变患者Foxp3mRNA相对表达量与宫颈病变严重程度呈正相关(r=0.697,P<0.05),RORγt mRNA的相对表达量与宫颈病变严重程度呈负相关(r=-0.657,P<0.05)。结论:HPV阳性患者宫颈发生病变与其Foxp3 mRNA表达量升高、RORγt mRNA表达量降低有关。
Objective:To investigate the level of Foxp3 mRNA,RORγt mRNA in patients of cervical lesion with HPV infection and analyze the correlation with the occurrence of the disease.Method:373 cases of patients with cervical lesions were selected as research object in our hospital from 2016-01 to 2017-06,HPV infection in 158 cases(including 40 patients with cervicitis,CINⅠ25 cases,CINⅡ 25 cases,CIN Ⅲ 26 cases,42 patients with cervical cancer)was examed by PCR and gene chip.At the same time a medical health 39 cases was enrolled as control group.Peripheral blood mononuclear cells(PBMCs)in RORγt,Foxp3 mRNA expression levels were detected by Real-time fluorescent quantitative reverse transcription-polymerase chain reaction(QRT-PCR).The expression of Foxp3 mRNA and RORγt mRNA in different groups of HPV-positive and HPV-negative correlation between Foxp3 mRNA,RORγt mRNA and cervical cervical severity,and the correlation between Foxp3 mRNA,RORγt mRNA and cervical cervical severity.Results:With the aggravation of cervical lesions,the positive rate of HPV increased.The relative expression of Foxp3 mRNA,RORγt mRNA in the cervical lesions of HPV positive groups was statistically significant(P<0.05).The relative expression of Foxp3 mRNA was not significantly different between the cervicitis group and the CINI group(P>0.05),and the other groups showed CIN I0.05),and the other groups showed CIN I>CINⅡ>CINⅢ>cervical cancer,the difference was statistically significant(P<0.05).The relative expression of Foxp3 mRNA,RORγt mRNA was not statistically significant in the cervical lesions of HPV negative group(P>0.05).HPV positive patients with cervical lesions,Foxp3 mRNA expression increased with the severity of cervical lesion(r=0.697,P<0.05);the relative expression of RORγt mRNA content decreased with increasing severity of cervical lesion(r=-0.657,P<0.05).Conclusion:The cervical lesions(with HPV infection)has a relationship with mRNA expression of Foxp3 increasing and RORγt descending in peripheral blood.
Objective:To investigate the level of Foxp3 mRNA,RORγt mRNA in patients of cervical lesion with HPV infection and analyze the correlation with the occurrence of the disease.Method:373 cases of patients with cervical lesions were selected as research object in our hospital from 2016-01 to 2017-06,HPV infection in 158 cases(including 40 patients with cervicitis,CINⅠ25 cases,CINⅡ 25 cases,CIN Ⅲ 26 cases,42 patients with cervical cancer)was examed by PCR and gene chip.At the same time a medical health 39 cases was enrolled as control group.Peripheral blood mononuclear cells(PBMCs)in RORγt,Foxp3 mRNA expression levels were detected by Real-time fluorescent quantitative reverse transcription-polymerase chain reaction(QRT-PCR).The expression of Foxp3 mRNA and RORγt mRNA in different groups of HPV-positive and HPV-negative correlation between Foxp3 mRNA,RORγt mRNA and cervical cervical severity,and the correlation between Foxp3 mRNA,RORγt mRNA and cervical cervical severity.Results:With the aggravation of cervical lesions,the positive rate of HPV increased.The relative expression of Foxp3 mRNA,RORγt mRNA in the cervical lesions of HPV positive groups was statistically significant(P<0.05).The relative expression of Foxp3 mRNA was not significantly different between the cervicitis group and the CINI group(P>0.05),and the other groups showed CIN I
引文
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5 尤亚红,YouYahong.调节性T淋巴细胞/辅助性T淋巴细胞17失衡在自身免疫性疾病中的研究进展[J].国际输血及血液学杂志,2015,38(6):541—545.
6 Etesam Z,Nemati M,Ebrahimizadeh M A,et al.Altered expression of specific transcription factors of Th17(RORrt,RORa)and treg lymphocytes(FOXP3)by peripheral blood mononuclear cells from patients with multiple sclerosis[J].Journal of Molecular Neuroscience,2016,60(1):1—8.
7 乐杰.妇产科学[M].北京:人民卫生出版社,2008:257—269.
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10 谭秋梅.HPV感染、阴道局部T淋巴细胞亚群与宫颈病变的关系研究[J].湖北医药学院学报,2016(6):557—560.
11 Schmidt A,Zhang XM,Joshi RN,et al.Human macrophages induce CD4(+)Foxp3(+)regulatory T cells via binding and re-release of TGF-β[J].Immunology&Cell Biology,2016,94(8):747—748.
12 张剑英,刘班,张毅敏,等.宫颈癌患者外周血中调节性T细胞的变化及其临床意义[J].中华微生物学和免疫学杂志,2015,35 (10):753—758.
13 Luo X,Tsun A,Yang J,et al.FOXP3+,treg cells and systems biology approaches to studying their function[M].Single Cell Sequencing and Systems Immunology.Springer Netherlands,2015:73—93.
14 Bhairavabhotla R,Kim Y C,Glass D D,et al.Transcriptome profiling of human Foxp3+regulatory T cells[J].Human Immunology,2016,77(2):201—202.
15 Park BV,Pan F.The role of nuclear receptors in regulation of Th17/Treg biology and its implications for diseases[J].Cell Mol Immunol,2015,12(5):533—542.
16 Ding Q,Zhao M,Bai C,et al.Inhibition of RORrt activity and Th17differentiation by a set of novel compounds[J].BMC Immunology,2015,16(1):1—9.
2 张倩,胡尚英,冯瑞梅,等.高危型人乳头瘤病毒感染变化与宫颈癌及癌前病变发病风险的15年前瞻队列随访研究[J].中华肿瘤杂志,2016,38(10):792—797.
3 Asih T S,Lenhart S,Wise S,et al.The dynamics of HPV infection and cervical cancer cells[J].Bulletin of Mathematical Biology,2016,78(1):1—17.
4 Song D,Li H,Li H,et al.Effect of human papillomavirus infection on the immune system and its role in the course of cervical cancer[J].Oncol Lett,2015,10(2):600—602.
5 尤亚红,YouYahong.调节性T淋巴细胞/辅助性T淋巴细胞17失衡在自身免疫性疾病中的研究进展[J].国际输血及血液学杂志,2015,38(6):541—545.
6 Etesam Z,Nemati M,Ebrahimizadeh M A,et al.Altered expression of specific transcription factors of Th17(RORrt,RORa)and treg lymphocytes(FOXP3)by peripheral blood mononuclear cells from patients with multiple sclerosis[J].Journal of Molecular Neuroscience,2016,60(1):1—8.
7 乐杰.妇产科学[M].北京:人民卫生出版社,2008:257—269.
8 揭伟霞,薛武进,史志华,等.宫颈上皮内瘤变与宫颈癌患者人乳头状瘤病毒感染的临床分析[J].中华医院感染学杂志,2016,26 (6):1 380—1 381.
9 Day PM,Schiller JT.The role of furin in papillomavirus infection[J].Future Microbiology,2015,4(10):1 255—1 256.
10 谭秋梅.HPV感染、阴道局部T淋巴细胞亚群与宫颈病变的关系研究[J].湖北医药学院学报,2016(6):557—560.
11 Schmidt A,Zhang XM,Joshi RN,et al.Human macrophages induce CD4(+)Foxp3(+)regulatory T cells via binding and re-release of TGF-β[J].Immunology&Cell Biology,2016,94(8):747—748.
12 张剑英,刘班,张毅敏,等.宫颈癌患者外周血中调节性T细胞的变化及其临床意义[J].中华微生物学和免疫学杂志,2015,35 (10):753—758.
13 Luo X,Tsun A,Yang J,et al.FOXP3+,treg cells and systems biology approaches to studying their function[M].Single Cell Sequencing and Systems Immunology.Springer Netherlands,2015:73—93.
14 Bhairavabhotla R,Kim Y C,Glass D D,et al.Transcriptome profiling of human Foxp3+regulatory T cells[J].Human Immunology,2016,77(2):201—202.
15 Park BV,Pan F.The role of nuclear receptors in regulation of Th17/Treg biology and its implications for diseases[J].Cell Mol Immunol,2015,12(5):533—542.
16 Ding Q,Zhao M,Bai C,et al.Inhibition of RORrt activity and Th17differentiation by a set of novel compounds[J].BMC Immunology,2015,16(1):1—9.