Prognostic risk model of LIHC T-cells based on scRNA-seq and RNA-seq and the regulation of the tumor immune microenvironment

Abstract

Abstract Background T-cell-related genes play a crucial role in LIHC development. However, a reliable prognostic profile based on risk models of these genes has yet to be identified. Methods Single-cell datasets from both tumor and normal tissue samples were obtained from the GEO database. We identified T-cell marker genes and developed a genetic risk model using the TCGA-LIHC dataset, which was subsequently validated with an independent GEO dataset. We also explored the relationship between risk model predictions and immune responses. Results We constructed a prognostic risk model using eight gene features identified through screening 860 T-cell marker genes via scRNA-seq and RNA-seq, which was subsequently integrated with the TCGA dataset. Its validity was independently confirmed using GEO and ICGC datasets. The TCGA dataset was stratified into high-risk and low-risk groups based on the risk model. Multivariate Cox regression analysis confirmed the risk score as an independent prognostic factor. GSEA indicated ribosomal transporter metabolism enrichment in the high-risk group and significant transcriptional activation in the low-risk group. ESTIMATE analysis showed higher ESTIMATE, immune, and stromal scores in the low-risk group, which also exhibited lower tumor purity than the high-risk group. Immunophenotyping revealed distinct patterns of immune cell infiltration and an immunosuppressive environment in the high-risk group. Conclusions This study introduces a T-cell marker-based prognostic risk model for LIHC patients. This model effectively predicted survival outcomes and immunotherapy effectiveness in LIHC patients, aligning with diverse immune responses and the distinct immunological profiles observed in the high-risk group.

Keywords

• scRNA
• Immune cells
• TME
• T cell maturation trajectory
• Prognostic risk modeling