载脂蛋白 E 甲基化与肝癌的免疫微环境相关。

Apoprotein E methylation is correlated with immune microenvironment in hepatocellular carcinoma.

机构信息

Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, P.R. China.

Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.

出版信息

Acta Oncol. 2023 Jun;62(6):550-559. doi: 10.1080/0284186X.2023.2225703. Epub 2023 Jun 23.

DOI:10.1080/0284186X.2023.2225703

PMID:37352133

Abstract

BACKGROUND

We aimed to evaluate the correlation of apoprotein E (APOE) transcription and its methylation with immune microenvironment in HCC patients.

MATERIAL AND METHODS

The expression profiles of APOE transcription, APOE methylation, and APOE protein were investigated comprehensive bioinformatic analyses. After that, the association between the immune activation of HCC and APOE transcription and methylation were analyzed. Finally, the prognostic role and immune correlation of the APOE protein in 92 HCC individuals was determined.

RESULTS

Based on data from TCGA, GEO, and ICGC datasets, the APOE mRNA was differentially expressed in HCC tissues compared with normal liver tissues. Further, APOE methylation was down-regulated in HCC tissues compared to normal liver tissues. APOE methylation was negatively correlated with APOE transcription in HCC (=-0.52, < 0.0001). Based on APOE methylation, the HCC patients were stratified into hypermethylation and hypomethylation subgroups as they exhibited different immune activation statuses. Further, HCC individuals with APOE hypermethylation had a closer immune correlation than those with hypomethylation. Notably, APOE transcription was associated with weak immune infiltrates and activation. Finally, over-expression of the APOE protein was correlated with better survival outcomes, but not correlated with PD-1 or CTLA4 protein in HCC revealed by immunohistochemistry.

CONCLUSION

APOE methylation had a closer correlation with immune cells than APOE mRNA, indicating that APOE methylation might play an important role in immune regulation in HCC.

摘要

背景

本研究旨在评估载脂蛋白 E（APOE）转录及其甲基化与 HCC 患者免疫微环境的相关性。

材料与方法

通过综合生物信息学分析，研究了 APOE 转录、APOE 甲基化和 APOE 蛋白的表达谱。然后，分析了 HCC 中 APOE 转录和甲基化与免疫激活之间的关联。最后，在 92 例 HCC 个体中，确定了 APOE 蛋白的预后作用和免疫相关性。

结果

基于 TCGA、GEO 和 ICGC 数据集的数据，与正常肝组织相比，HCC 组织中 APOE mRNA 表达存在差异。此外，与正常肝组织相比，HCC 组织中 APOE 甲基化水平下调。APOE 甲基化与 HCC 中的 APOE 转录呈负相关（=-0.52，<0.0001）。根据 APOE 甲基化情况，将 HCC 患者分为高甲基化和低甲基化亚组，他们表现出不同的免疫激活状态。此外，与低甲基化组相比，APOE 高甲基化的 HCC 患者具有更密切的免疫相关性。值得注意的是，APOE 转录与较弱的免疫浸润和激活有关。最后，通过免疫组化发现，APOE 蛋白的过表达与更好的生存结局相关，但与 HCC 中的 PD-1 或 CTLA4 蛋白无关。