Construction of a new mitochondria-associated gene set model based on transcriptomic sequencing data to assess hepatocellular carcinoma immune, prognosis, and therapeutic characteristics
10.3760/cma.j.cn112309-20240303-00065
- VernacularTitle:基于转录组测序数据构建线粒体相关基因模型以评估肝细胞癌免疫、预后和治疗特征
- Author:
Ting TANG
1
;
Yubo LI
;
Xintong ZHANG
;
Yanfen HU
;
Hao WU
;
Jianjun ZHU
;
Li LI
;
Ming LIU
Author Information
1. 山西医科大学基础医学院医学细胞生物与遗传学教研室，太原 030001
- Publication Type:Journal Article
- Keywords:
Hepatocellular carcinoma;
Mitochondria-related genes;
TCGA;
Transcriptome sequencing;
Prognosis
- From:
Chinese Journal of Microbiology and Immunology
2025;45(1):53-63
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To construct a model of mitochondria-related genes (Mito-RGs) in hepatocellular carcinoma (HCC), and predict the immune, prognostic and therapeutic characteristics of HCC based on the model, so as to provide a new idea for the diagnosis and treatment of HCC.Methods:The expression profiles of HCC and corresponding clinical information were obtained from the Cancer Genome Atlas (TCGA) database. Univariate Cox regression, Least Absolute Shrinkage and Selection Operator (LASSO) regression and multivariate Cox regression were used to construct a prognostic model of HCC based on Mito-RGs, and the International Cancer Genome Consortium-Liver Cancer-RIKEN-Japan ICGC-LIRI-JP dataset were used for validation. GO and KEGG analyses were performed to investigate the signaling pathways enriched for differentially expressed genes in the high- and low-risk groups. Immune infiltration was assessed using CIBERSORT. Single-cell data were used to study the proportion of immune cells in high- and low-risk groups of HCC samples and the relationship with cell proliferation. Cellminer was used to assess the relationship between risk score models and drug sensitivity.Results:A risk-prognostic model of HCC containing seven Mito-RGs ( DTYMK, ACADS, HMGCS2, CYP27A1, TOMM40L, STOM, and AKR1B10) was constructed. High-risk HCC patients had a worse prognosis. Genes upregulated in the high- and low-risk groups of differentially expressed genes were enriched in cell cycle and metabolism-related pathways. Single-cell data showed higher proportions of CD8 + T cells, macrophages and monocytes, and proliferating cells in the high-risk group. CIBERSORT analysis suggested that Treg cells and M0 macrophages were more abundant in the high-risk group, whereas CD8 + T cells and CD4 + memory T cells were less abundant. Patients in the high-risk group were more sensitive to myeloid cell leukemia sequence 1 inhibitor, vincristine, phosphatidylinositol kinase beta subunit inhibitor, and aurora kinase A, while trametinib, selumetinib, extracellular regulated protein kinase, and mitogen-activated extracellular signal-regulated kinase were more effective in the low-risk group. Conclusion:The constructed Mito-RGs model is capable of providing a more accurate assessment of the prognosis and the degree of immune cell infiltration in HCC patients.
