TIPE2和FOXP3在肝癌和肝硬化患者肝组织中的表达及意义

doi:10.3969/j.issn.1004-583X.2025.05.005

临床荟萃 ›› 2025, Vol. 40 ›› Issue (5): 412-416.doi: 10.3969/j.issn.1004-583X.2025.05.005

TIPE2和FOXP3在肝癌和肝硬化患者肝组织中的表达及意义

孔丽^1a(), 赵素贤^1a, 张莹^1a, 金萌^1b, 王闪闪², 任伟光^1a, 张玉果³, 孔令波^1a, 韩芳^1a, 纪雷^1a

1.河北医科大学第三医院 a.中西医结合肝病科/河北省慢性肝病肝纤维化机制研究重点实验室; b.中医科,河北石家庄 050051
2.邯郸中心医院感染科,河北邯郸 056001
3.河北医科大学第一医院肝病科, 河北石家庄 300402

收稿日期:2025-02-27 出版日期:2025-05-20 发布日期:2025-05-23
通讯作者: 孔丽 E-mail:kongliyouxiang@sina.com
基金资助:
河北省科技计划民生科技专项——TIPE2在肝癌发生发展中的作用及免疫调控机制研究(20377775D);河北省医学科学研究课题——TIPE2及相关分子在肝细胞癌癌前病变患者中的变化及诊预测价值(20221175)

Expression levels of TIPE2 and FOXP3 in patients with hepatocellular carcinoma and cirrhosis and their clinical significance

Kong Li^1a(), Zhao Suxian^1a, Zhang Ying^1a, Jin Meng^1b, Wang Shanshan², Ren Weiguang^1a, Zhang Yuguo³, Kong Lingbo^1a, Han Fang^1a, Ji Lei^1a

1a. Department of Traditional and Western Medical Hepatology/Department of Key Laboratory of Chronic Liver Disease and Liver Fibrosis Reasearch of Hebei Provincial, b. Department of Traditional Chinese Medicine, the Third Hospital of Hebei Medical University, Shijiazhuang 050051, China
2. Department of Infectious Diseases, Handan Central Hospital, Handan 056001, China
3. The First Hospital of Hebei Medical University, Shijiazhuang 300402, China

Received:2025-02-27 Online:2025-05-20 Published:2025-05-23
Contact: Kong Li E-mail:kongliyouxiang@sina.com

摘要/Abstract

摘要：

目的分析肝癌和肝硬化患者肝组织中肿瘤坏死因子α诱导蛋白8样分子2(tumor necrosis factor-α-induced protein 8-like 2,TIPE2)和FOXP3 mRNA及蛋白的表达情况,探讨TIPE2和FOXP3在肝硬化和肝癌发生发展中的作用。方法收集肝癌和肝硬化患者手术切除的肝组织60例,分别应用免疫组化法和RT-PCR法检测肝组织中TIPE2和FOXP3 mRNA及蛋白的表达水平,并与肝组织病理分级、甲胎蛋白(alpha-fetoprotein,AFP)、天冬氨酸氨基转移酶(aspartate transaminase, AST)/丙氨酸氨基转移酶(alanine amiotransferase, ALT)比值、中性粒细胞/淋巴细胞比值(neutrophil-to-lymphocyte ratio,NLR)等多项临床资料进行相关性分析。结果肝癌患者较肝硬化患者肝组织中TIPE2 mRNA和蛋白表达明显降低(P<0.01),而FOXP3 mRNA和蛋白表达明显升高(P<0.01);肝组织TIPE2蛋白和mRNA表达水平与FOXP3表达水平呈负相关(P<0.05,P<0.01);TIPE2和FOXP3表达与肝癌组织分化程度密切相关,分化程度越低TIPE2下调越明显,而FOXP3上调越显著;同时TIPE2表达程度与血清AFP水平、AST/ALT比值、中性粒细胞数量和NLR呈负相关。结论 TIPE2可能通过负性调控FOXP3⁺Treg细胞介导的免疫反应参与了肝脏疾病的发生和进展,在肝癌的发生中可能发挥负性调控作用。

关键词: 肝疾病, TIPE2, FOXP3, 肝组织, 免疫调节

Abstract:

Objective To detect the mRNA and protein levels of tumor necrosis factor-α-induced protein 8-like 2 (TIPE2) and FOXP3 in patients with cirrhosis and hepatocellular carcinoma (HCC) and their clinical significances. Methods A total of 60 surgical specimens from patients with HCC and cirrhosis were enrolled. The expression levels of TIPE2 and FOXP3 in liver tissues were evaluated using immunohistochemistry and real-time reverse transcription-polymerase chain reaction (RT-PCR). The correlation of TIPE2 and FOXP3 levels with pathological grading, alpha-fetoprotein (AFP), aspartate transaminase/alanine aminotransferase (AST/ALT), neutrophil-to-lymphocyte ratio (NLR) and other clinical data was analyzed. Results The mRNA and protein levels of TIPE2 were significantly down-regulated (P<0.01), while those of FOXP3 were significantly up-regulated in HCC tissues compared to cirrhosis tissues (P<0.01). Importantly, the mRNA and protein levels of TIPE2 were negatively correlated with FOXP3 expressions (P<0.05 and P<0.01, respectively). Furthermore, TIPE2 and FOXP3 levels were correlated with pathological grade of HCC tissue, and lower TIPE2 and higher FOXP3 levels indicated lower differentiation level. TIPE2 expression was negatively correlated with the AFP level, AST/ALT ratio, neutrophil count and neutrophil-to-lymphocyte ratio (NLR). Conclusion TIPE2 is involved in the liver diseases by negatively regulating the function of FOXP3⁺ Tregs-induced immune response, and negatively participates in the occurrence of HCC.

Key words: liver diseases, TIPE2, FOXP3, liver tissue, immunomodulation

中图分类号:

R575

孔丽, 赵素贤, 张莹, 金萌, 王闪闪, 任伟光, 张玉果, 孔令波, 韩芳, 纪雷. TIPE2和FOXP3在肝癌和肝硬化患者肝组织中的表达及意义[J]. 临床荟萃, 2025, 40(5): 412-416.

Kong Li, Zhao Suxian, Zhang Ying, Jin Meng, Wang Shanshan, Ren Weiguang, Zhang Yuguo, Kong Lingbo, Han Fang, Ji Lei. Expression levels of TIPE2 and FOXP3 in patients with hepatocellular carcinoma and cirrhosis and their clinical significance[J]. Clinical Focus, 2025, 40(5): 412-416.

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链接本文: https://lchc.magtechjournal.com/CN/10.3969/j.issn.1004-583X.2025.05.005

https://lchc.magtechjournal.com/CN/Y2025/V40/I5/412

图/表 4

表1 3组肝组织中TIPE2和FOXP3蛋白表达水平比较

Tab.1 Protein levels of TIPE2 and FOXP3 in liver tissues

组别	例数	TIPE2阳性细胞	TIPE2(MOD值)	FOXP3阳性细胞	FOXP3(MOD值)
肝癌组	30	2.25±1.24^#△	0.063±0.015^#△	5.66±2.28^#△	0.142±0.018^#△
肝硬化组	30	4.25±1.48^#	0.087±0.012^#	4.31±1.22^#	0.116±0.031^*
对照组	11	6.09±1.75	0.129±0.021	2.64±1.28	0.088±0.017
F值		21.468	44.168	9.945	17.884
P值		<0.01	<0.01	<0.01	<0.01

图1 TIPE2和FOXP3蛋白在肝癌及肝硬化组织中的表达(×400) a.对照组TIPE2;b.肝硬化组TIPE2;c.肝癌组TIPE2;d.对照组FOXP3;e.肝硬化组FOXP3;f.肝癌组FOXP3

Fig.1 Protein expressions of TIPE2 and FOXP3 in HCC and cirrhosis tissues (×400) Fig.a represents TIPE2 in the control group; Fig.b represents TIPE2 in the cirrhosis group; Fig.c represents TIPE2 in the HCC group; Fig.d represents FOXP3 in the control group; Fig.e represents FOXP3 in the cirrhosis group; Fig.f represents FOXP3 in the HCC group

表2 TIPE2和FOXP3 mRNA在肝癌及肝硬化患者肝组织中的表达

Tab.2 The mRNA levels of TIPE2 and FOXP3 in HCC and liver cirrhosis tissues

组别	例数	TIPE2 mRNA		FOXP3 mRNA
组别	例数	阳性率[例(%)]	数值	阳性率[例(%)]	数值
肝癌组	30	16(53.33)	0.35±0.21	26(86.67)	4.64±1.08
肝硬化组	30	23(76.67)	0.45±0.15	21(70.00)	3.16±1.02
统计值		χ²=3.590	t=2.122	χ²=2.455	t=5.457
P值		>0.05	<0.05	>0.05	<0.01

表3 肝癌组织TIPE2和FOXP3蛋白和mRNA表达与肝癌病理分级关系

Tab.3 Correlation of the protein and mRNA levels of TIPE2 and FOXP3 in HCC tissues with pathological grading

组别	例数	TIPE2蛋白	TIPE2 mRNA	FOXP3蛋白	FOXP3 mRNA
Ⅰ级	6	3.87±1.09	0.58士0.12	4.12±2.10	3.08±1.09
Ⅱ级	15	2.31±0.76^#	0.26士0.08^#	5.38±1.06	4.56±1.02^#
Ⅲ级	9	1.25±0.45^#△	0.10士0.02^#△	6.69±1.35^*	5.48±1.05^#
F值		8.752	24.713	3.519	5.794
P值		<0.01	<0.01	<0.05	<0.01

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TIPE2和FOXP3在肝癌和肝硬化患者肝组织中的表达及意义

Expression levels of TIPE2 and FOXP3 in patients with hepatocellular carcinoma and cirrhosis and their clinical significance

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