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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:

32卷

期数:

2026年01期

页码:

23-31,38

栏目:

肿瘤疾病专题

出版日期:

2026-01-20

文章信息/Info

Title:

Preliminary study on the effects and mechanism of DDIT4 on immune cell infiltration in hepatocellular carcinoma

文章编号:

1006-8147(2026)01-0023-10

作者:

王添; 丁子特; 胡飞云; 车娜; 董学易; 张丹芳

（天津医科大学基础医学院病理学教研室，天津300070）

Author(s):

WANG Tian;  DING Zite;  HU Feiyun;  CHE Na;  DONG Xueyi;  ZHANG Danfang

（Department of Pathology， College of Basic Medical Sciences， Tianjin Medical University， Tianjin 300070， China）

关键词:

DNA损伤诱导转录物4; 肝细胞肝癌; 免疫细胞浸润; P53

Keywords:

DNA damage inducible transcript 4; hepatocellular carcinoma; immune cell infiltration; P53

分类号:

R735.7

DOI:

10.20135/j.issn.1006-8147.2026.01.0023

文献标志码:

A

摘要:

目的：研究肝细胞肝癌（HCC）中DNA损伤诱导转录物4（DDIT4）表达对免疫细胞浸润的影响及其机制。方法：使用数据库分析DDIT4的表达和预后及临床特征的关系、DDIT4参与的信号通路以及DDIT4表达与免疫细胞表达水平之间的关系；通过Western blotting实验检测DDIT4表达对P53信号通路的影响；通过Transwell实验检测DDIT4表达对HCC细胞迁移、侵袭的影响。结果：HCC中DDIT4高表达时抗肿瘤免疫细胞浸润减少（P＜0.05），免疫抑制细胞浸润增多（P＜0.05）；同时DDIT4表达与P53信号通路呈正相关（P＜0.05）。免疫印迹结果显示：HCC中DDIT4低表达且处于乏氧微环境时P53蛋白表达最少，其中，在HepG2细胞系中，与SH-Control组相比，SH-Control CoCl2组、SH-DDIT4组P53蛋白表达增加（t=20.81、24.59，均P＜0.05）；与SH-Control CoCl2组相比，SH-DDIT4 CoCl2组P53蛋白表达增加（t=25.50，P＜0.05）；与SH-DDIT4组相比，SH-DDIT4 CoCl2组P53蛋白表达增加（t=13.86，P＜0.05）。在MHCCLM3细胞系中，与EX-Control组相比，EX-Control CoCl2组、EX-DDIT4组P53蛋白表达增加（t=18.89、23.29，均P＜0.05）；与EX-Control CoCl2组相比，EX-DDIT4 CoCl2组P53蛋白表达减少（t=5.739，P＜0.05）；与EX-DDIT4组相比，EX-DDIT4 CoCl2组P53蛋白表达增加（t=15.36，P＜0.05）。Transwell实验显示，乏氧微环境DDIT4高表达增强了HCC细胞迁移和侵袭能力，其中，在HepG2细胞系中，与SH-Control组相比，SH-DDIT4组迁移、侵袭细胞数目减少（t=7.896、7.604，均P＜0.05）；与SH-Control CoCl2组相比，SH-DDIT4 CoCl2组的迁移、侵袭细胞数目减少（t=18.20、15.12，均P＜0.05）。在MHCCLM3细胞系中，与EX-Control组相比，EX-DDIT4组迁移、侵袭细胞数目增加（t=11.17、15.23，均P＜0.05）；与EX-Control CoCl2组相比，EX-DDIT4 CoCl2组迁移、侵袭细胞数目增加（t=9.886、16.38，均P＜0.05）。结论：乏氧微环境中HCC通过上调DDIT4，抑制P53蛋白，增加免疫抑制细胞浸润和减少免疫促进细胞浸润。

Abstract:

Objective： To study the effect of DNA damage inducible transcript 4 （DDIT4） expression on immune cell infiltration and its mechanism in hepatocellular carcinoma （HCC）. Methods： The relationship between DDIT4 expression and prognosis， clinical characteristics，signaling pathways involved in DDIT4， and the correlation between DDIT4 expression and immune cell expression levels were investigated using database analysis. The effect of DDIT4 expression on the P53 signaling pathway was detected using Western blotting experiments. The impact of DDIT4 expression on migration and invasion of HCC cells were assessed using Transwell assays. Results： In HCC， the high expression of DDIT4 decreased the infiltration of anti-tumor immune cells（P<0.05） and increased the infiltration of immunosuppressive cells（P<0.05）； meanwhile， the expression of DDIT4 was positively correlated with the P53 signaling pathway（P<0.05）. The results of Western blotting showed that DDIT4 exhibited low expression in HCC， and the expression of P53 protein was the lowest under hypoxic microenvironment conditions. Specifically， in the HepG2 cell line， compared with the SH-Control group， the P53 protein expression increased in the SH-Control CoCl2 group and SH-DDIT4 group （t=20.81， 24.59， both P<0.05）； compared with the SH-Control CoCl2 group， the P53 protein expression increased in the SH-DDIT4 CoCl2 group （t= 25.50， P<0.05）； and compared with the SH-DDIT4 group， the P53 protein expression increased in the SH-DDIT4 CoCl2 group （t=13.86， P<0.05）. In the MHCCLM3 cell line， compared with the EX-Control group， the P53 protein expression increased in the EX-Control CoCl2 group and EX-DDIT4 group （t=18.89，23.29， both P<0.05）； compared with the EX-Control CoCl2 group， the P53 protein expression decreased in the EX-DDIT4 CoCl2 group （t=5.739， P<0.05）； and compared with the EX-DDIT4 group， the P53 protein expression increased in the EX-DDIT4 CoCl2 group （t=15.36， P<0.05）. The Transwell assay demonstrated that high expression of DDIT4 under hypoxic microenvironment conditions enhanced the migration and invasion capabilities of HCC cells. Specifically， in the HepG2 cell line， compared with the SH-Control group， the number of migrating and invading cells decreased in the SH-DDIT4 group （t=7.896， 7.604， both P<0.05）； compared with the SH-Control CoCl2 group， the number of migrating and invading cells decreased in the SH-DDIT4 CoCl2 group （t=18.20， 15.12， both P<0.05）. In the MHCCLM3 cell line， compared with the EX-Control group， the number of migrating and invading cells increased in the EX-DDIT4 group （t=11.17， 15.23， both P<0.05）； compared with the EX-Control CoCl2 group， the number of migrating and invading cells increased in the EX-DDIT4 CoCl2 group （t=9.886， 16.38， both P<0.05）. Conclusion： HCC in a hypoxic microenvironment increases immunosuppressive cell infiltration and decreases immune-promoting cell infiltration through up-regulation of DDIT4 inhibiting P53 protein.

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备注/Memo

备注/Memo:

基金项目:国家自然科学基金（82373278）
作者简介:王添（1998-），男，硕士在读，研究方向：病理学；
通信作者:张丹芳，E-mail： zhangdf@tmu.edu.cn。

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更新日期/Last Update: 2026-01-15