Exploratory study on the role of tumor microenvironment-related gene CCR7 in Cuproptosis and its potential as a prognostic marker for liver cancer
10.3760/cma.j.cn114452-20240507-00227
- VernacularTitle:肿瘤微环境相关基因CCR7在肝癌铜死亡中的作用及其作为肝癌预后标志物的探索性研究
- Author:
Yuan CHEN
1
;
Yunhui LI
;
Jing LIANG
;
Li WANG
;
Renlong ZHU
;
Jiayue MA
;
Yajie WANG
Author Information
1. 北京大学地坛医院教学医院检验科，北京 100015
- Keywords:
Receptors, CCR7;
Tumor microenvironment;
Liver cancer;
Cuproptosis
- From:
Chinese Journal of Laboratory Medicine
2024;47(10):1169-1177
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the interplay between tumor microenvironment (TME)-associated genes, cuproptosis, and the prognosis of liver cancer through transcriptome sequencing and functional genomics analysis.Methods:Employing a hybrid approach that integrates bioinformatics with fundamental experimental research, we utilized the TCGA database to acquireexpression profiles and clinical-pathological information from 424 liver hepatocellular carcinoma patients. We evaluated ImmuneScore and StromalScore to categorize patients into high and low groups, subsequently identifying differentially expressed genes (DEG) at the intersection of these groups. Core DEG were identified through univariate Cox regression analysis and protein-protein interaction (PPI) network analysis. The association between the expression levels of core genes and the survival time of liver cancer patients was analyzed using the R language and Kaplan-Meier analysis, and verified using the Kaplan-Meier Plotter online database. We established a cuproptosis cell model and performed RNA-seq to examine gene expression alterations during copper-induced cell death, followed by in vitro cell experiments for verification.Results:A total of 1 701 and 2 041 DEG were llinked t ImmuneScore and StromalScore, respectively, encompassing 1 134 commonly upregulated genes and 60 commonly downregulated genes. The top 30 core genes from the PPI network's dominant nodes were cross-referenced with univariate Cox regression results, leading to the identification of the pivotal immune gene CCR7. CCR7 mRNA expression levels were higher in hepatocellular carcinoma tissues than in normal tissues ( P<0.05). Patients with high expression of CCR7 in liver cancer had a longer overall survival compared to those with low expression ( P=0.003). Treatment with elesclomol-CuCl2significantly curtailed the survival of hepatocellular carcinoma cel ( P<0.001). RNA-seq data from the cuproptosis model indicated a downregulation of CCR7 expression during the onset of cuproptosis [|log 2(FC)|=2.27, P<0.001], and downregulation of CCR7 expression enhanced the sensitivity of hepatocellular carcinoma cells to cuproptosis inducers. Conclusion:The TME-related gene CCR7 is implicated in cuproptosis, and its downregulation might facilitate the process in liver cancer.CCR7 holds potential as a biomarker for liver cancer prognosis.
