肿瘤坏死因子α诱导蛋白8样分子2和叉头样转录因子3 mRNA在原发性肝癌患者外周血单个核细胞中的表达及意义

孔丽; 张玉卓; 金萌; 王闪闪; 杜静华; 张玉果; 王荣琦; 任伟光; 南月敏

doi:10.3969/j.issn.1001-5256.2019.12.016

肿瘤坏死因子α诱导蛋白8样分子2和叉头样转录因子3 mRNA在原发性肝癌患者外周血单个核细胞中的表达及意义

DOI: 10.3969/j.issn.1001-5256.2019.12.016

1. 河北医科大学第三医院肝病科,河北省慢性肝病肝纤维化机制研究重点实验室
2. 河北省中医药科学院
3. 河北医科大学第三医院中医科

基金项目:

河北省卫生计生委医学科研重点课题(ZL20140032)；河北省中医药管理局课题(2014142)；

详细信息

中图分类号: R735.7
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出版历程
- 收稿日期: 2019-09-20
- 出版日期: 2019-12-20

mRNA expression and significance of tumor necrosis factor-alpha-induced protein 8-like 2 and forkhead box P3 in peripheral blood mononuclear cells in patients with primary liver cancer

Department of Hepatology,Third Hospital of Hebei Medical University

Research funding:

摘要

摘要: 目的探讨原发性肝癌患者外周血单个核细胞（PBMC）中肿瘤坏死因子α诱导蛋白8样分子2（TIPE2）和CD4+CD25+调节性T淋巴细胞（Treg）叉头样转录因子3（Foxp3）的表达及相关关系。方法选择2014年1月-2016年12月在河北医科大学第三医院门诊及住院的原发性肝癌患者55例,同期选择健康自愿者35例为对照组。检测2组PBMC中TIPE2 mRNA和Foxp3mRNA的表达水平,并与肝脏血清生化指标、AFP、血白细胞及肿瘤大小、数量等进行相关性分析。符合正态分布的计量资料2组间比较采用t检验;不符合正态分布的计量资料2组间比较采用Mann-Whitney U检验。计数资料2组间比较采用χ2检验;相关分析采用Pearson相关性检验。结果 2组患者ALT、AST、AST/ALT、TBil、WBC、AFP水平比较,差异均有统计学意义（P值均<0. 05）。原发性肝癌组患者TIPE2 mRNA表达较对照组明显降低（0. 396±0. 174 vs 1. 045±0. 330,t=12. 187,P <0. 01）;而Foxp3 mRNA表达较对照组明显升高（4. 49...
- 肝肿瘤 /
- 肿瘤坏死因子α诱导蛋白8样分子2 /
- 叉头样转录因子3 /
- 外周血单个核细胞
Abstract: Objective To investigate the mRNA expression of tumor necrosis factor-alpha-induced protein 8-like 2( TIPE2) and forkhead box P3( Foxp3) of CD4+CD25+regulatory T cells( Tregs) in peripheral blood mononuclear cells( PBMCs) and their correlation in patients with primary liver cancer. Methods A total of 55 patients with primary liver cancer who visited the outpatient service or were hospitalized in Third Hospital of Hebei Medical University from January 2014 to December 2016 were enrolled as primary liver cancer group,and 35 healthy volunteers were enrolled as control group. The mRNA expression of TIPE2 and Foxp3 in PBMCs was measured,and their correlation with serum biochemical parameters for the liver,alpha-fetoprotein( AFP),blood leukocytes,and tumor size and number was analyzed. The t-test was used for comparison of continuous data between two groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between two groups,and the Pearson correlation analysis was used to investigate correlation. Results There were significant differences between the two groups in alanine aminotransferase( ALT),aspartate aminotransferase( AST),AST/ALT ratio,total bilirubin,white blood cell count,and AFP( all P < 0. 05). Compared with the control group,the primary liver cancer group had significantly lower mRNA expression of TIPE2( 0. 396 ± 0. 174 vs 1. 045 ± 0. 330,t = 12. 187,P < 0. 01) and significantly higher mRNA expression of Foxp3( 4. 498 ± 1. 672 vs 1. 922 ±1. 297,t = 7. 746,P < 0. 01). The mRNA expression of TIPE2 was negatively correlated with serum levels of ALT and AST,AST/ALT ratio,and AFP level( r =-0. 752,-0. 833,-0. 992,and-0. 848,all P < 0. 05),while the mRNA expression of Foxp3 was positively correlated with serum levels of ALT and AST,AST/ALT ratio,and AFP level( r = 0. 449,0. 536,0. 843,and 0. 640,all P < 0. 05). ThemRNA expression of TIPE2 was negatively correlated with that of Foxp3( r =-0. 821,P < 0. 01). Conclusion Liver cancer patients have downregulated mRNA expression of TIPE2 and upregulated mRNA expression of Foxp3,which is correlated with the degree of hepatocellular injury and AFP level. The TIPE2 gene may be involved in the pathogenesis of liver cancer by negative regulation of Treg-mediated immune response.
- liver neoplasms /
- TIPE2 /
- Foxp3 /
- peripheral blood mononuclear cell

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参考文献(21)

[1] SUN H,GONG S,CARMODY RJ,et al. TIPE2,a negative regulator of innate and adaptive immunity that maintains immune homeostasis[J]. Cell,2008,133(3):415-426.

[2] LI T,WANG W,GONG S,et al. Genome-wide analysis reveals TNFAIP8L2 as an immune checkpoint regulator of inflammation and metabolism[J]. Mol Immunol,2018,99:154-162.

[3] GUS-BRAUTBAR Y,JOHNSON D,ZHANG L,et al. The anti-inflammatory TIPE2 is an inhibitor of the oncogenic Ras[J].Mol Cell,2012,45(5):610-618.

[4] REN H,LI X. Expression and role of FOXP3 in different human tumors[J]. Chin J Clin Oncol,2017,44(10):508-514.(in Chinese)任贺，李鑫．转录因子FOXP3在不同肿瘤中的表达及功能研究进展[J]．中国肿瘤临床，2017,44(10):508-514.

[5] LUAN YY,YAO YM,ZHANG L,et al. Expression of tumor necrosis factor-αinduced protein 8 like-2 contributes to the immunosuppressive property of CD4(+)CD25(+)regulatory T cells in mice[J]. Mol Immunol,2011,49(1-2):219-226.

[6] Chinese Societies of Liver Cancer Clinical Oncology,Chinese Anti-Cancer Association Liver Cancer Study Group,Chinese Society of Hepatology. Expert consensus on standardization of the management of primary liver cancer[J]. J Clin Hepatol,2009,25(2):83-92.(in Chinese)中国抗癌协会肝癌专业委员会，中国抗癌协会临床肿瘤学协作专业委员会，中华医学会肝病学分会肝癌学组．原发性肝癌规范化诊治的专家共识[J]．临床肝胆病杂志，2009,25(2):83-92.

[7] LI Z,GUO C,LIU X,et al. TIPE2 suppresses angiogenesis and non-small cell lung cancer(NSCLC)invasiveness via inhibiting Rac1 activation and VEGF expression[J]. Oncotarget,2016,7(38):62224-62239.

[8] WU DD,LIU SY,GAO YR,et al. Tumour necrosis factor-α-induced protein 8-like 2 is a novel regulator of proliferation,migration,and invasion in human rectal adenocarcinoma cells[J]. J Cell Mol Med,2019,23(3):1698-1713.

[9] JIA W,LI Z,CHEN J,et al. TIPE2 acts as a biomarker for tumor aggressiveness and suppresses cell invasiveness in papillary thyroid cancer(PTC)[J]. Cell Biosci,2018,8:49.

[10] KONG L,JIN M,ZHAO SX. Recent advances in tumor necrosis factor-alpha-induced protein 8-like 2 for regulating on tumor immunity[J]. J Clin Hepatol,2016,32(12):13-16.(in Chinese)孔丽，金萌，赵素贤．肿瘤坏死因子α诱导蛋白8样分子2在肝脏及胃肠肿瘤中的研究进展[J]．临床肝胆病杂志，2016,32(12):13-16.

[11] XI W,HU Y,LIU Y,et al. Roles of TIPE2 in hepatitis B virusinduced hepatic inflammation in humans and mice[J]. Mol Immunol,2011,48(9-10):1203-1208.

[12] FAN YC,ZHANG YY,WANG N,et al. Tumor necrosis factor-α-induced protein 8-like 2(TIPE2)is associated with immune phases of patients with chronic hepatitis B[J]. Oncotarget,2017,8(19):30781-30792.

[13] KONG L,LIU K,ZHANG YZ,et al. Downregulation of TIPE2mRNA expression in peripheral blood mononuclear cells from patients with chronic hepatitis C[J]. Hepatol Int,2013,7(3):844-849.

[14] KONG L,JIN M,WANG WZ,et al. The mRNA expression of TIPE2,Foxp3,and CTLA-4 in peripheral blood mononueleated cells in patients with chronic hepatitis C and their clinical significance[J]. J Clin Hepatol,2019,35(2):323-327.(in Chinese)孔丽，金萌，王卫真，等．TIPE2、Foxp3、CTLA-4 mRNA在慢性丙型肝炎患者外周血单个核细胞中的表达及临床意义[J]．临床肝胆病杂志，2019,35(2):323-327.

[15] WANG Y,JIANG Y,ZHOU J,et al. Hepatitis C virus promotes hepatocellular carcinogenesis by targeting TIPE2,a new regulator of DNA damage response[J]. Tumour Biol,2016,37(11):15265-15274.

[16] CAO X,ZHANG L,SHI Y,et al. Human tumor necrosis factor(TNF)-alpha-induced protein 8-like 2 suppresses hepatocellular carcinoma metastasis through inhibiting Rac1[J]. Mol Cancer,2013,12(1):149.

[17] WANG L,CHEN C,FENG S,et al. TIPE2 suppresses growth and aggressiveness of hepatocellular carcinoma cells through downregulation of the phosphoinositide 3-kinase/AKT signaling pathway[J]. Mol Med Rep,2018,17(5):7017-7026.

[18] KUMAR P,BHATTACHARYA P,PRABHAKAR BS. A comprehensive review on the role of co-signaling receptors and Treg homeostasis in autoimmunity and tumor immunity[J]. J Autoimmun,2018,95:77-99.

[19] OU X,ZHANG GT,TIAN PK,et al. Forkhead box P3 gene silencing inhibits the expression of chemokines and chemokine receptors associated with cell growth,migration,and apoptosis in hepatocellular carcinoma cells[J]. Exp Ther Med,2019,18(2):1091-1098.

[20] FAN T,HUANG X,LIU C,et al. Egress of murine regulatory T cells from the thymus requires TIPE2[J]. Biochem Biophys Res Commun,2018,500(2):376-383.

[21] LIU R,LIU C,LIU C,et al. TIPE2 in dendritic cells inhibits the induction of pTregs in the gut mucosa[J]. Biochem Biophys Res Commun,2019,509(4):911-917.

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