Construction of CD8+T cell-associated Risk Model in Hepatocellular Carcinoma Based on Bulk and Single-cell RNA-seq Data
10.13865/j.cnki.cjbmb.2025.08.1145
- VernacularTitle:基于整体和单细胞RNA测序数据构建肝细胞癌CD8+T细胞相关风险模型
- Author:
Xin-Tong ZHANG
1
;
Jian-Jun ZHU
;
Jin WU
;
Hao WU
;
Fan LU
;
Wen-Tao ZHANG
;
Jing-Jia CHANG
;
Ting TANG
;
Zhi-Gao OU
;
Feng-Feng JIA
;
Li LI
;
Peng-Fei YU
;
Ming LIU
Author Information
1. 山西医科大学基础医学院细胞生物学与医学遗传学教研室,太原 030001;上海交通大学基础医学院生物化学与分子细胞生物学系,上海 200025
- Publication Type:Journal Article
- Keywords:
hepatocellular carcinoma(HCC);
CD8+T cell;
risk scoring model;
tumor immunity;
drug sensitivity
- From:
Chinese Journal of Biochemistry and Molecular Biology
2025;41(10):1511-1528
- CountryChina
- Language:Chinese
-
Abstract:
Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8+T cell immune infiltration and immune suppression.We constructed a CD8+T cells related risk score model to pre-dict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8+T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS2,and TN-FRSF1B was constructed.The risk score model was well validated through an independent external validation co-hort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differ-ences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P＜0.0001)and lower CD8+T cells infiltration(P＜0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P＜0.01).Drug sensitivity a-nalysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene mod-el was verified by immunohistochemistry.In summary,the establishment and validation of a CD8+T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.
