Integration of single-cell and bulk RNA sequencing identifies and validates T cell-related prognostic model in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is a lethal malignancy, and predicting patient prognosis remains a significant challenge in clinical treatment. T cells play a crucial role in the tumor microenvironment, influencing tumorigenesis and progression. In this study, we constructed a T cell-related prognostic model for HCC. Using single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database, we identified 6,281 T cells from 10 HCC patients and subsequently identified 855 T cell-related genes. Comprehensive analyses were conducted on T cells and their associated genes, including enrichment analysis, cell-cell communication, trajectory analysis, and transcription factor analysis. By integrating scRNA-seq and bulk RNA-seq data with prognostic information from The Cancer Genome Atlas (TCGA), we identified T cell-related prognostic genes and constructed a model using LASSO regression. The model, incorporating PTTG1, LMNB1, SLC38A1, and BATF, was externally validated using the International Cancer Genome Consortium (ICGC) database. It effectively stratified patients into high- and low-risk groups based on risk scores, revealing significant differences in immune cell infiltration between these groups. Differential expression levels of PTTG1 and BATF between HCC and adjacent non-tumor tissues were further validated by immunohistochemistry (IHC) in 25 patient tissue samples. Moreover, a Cox regression analysis was performed to integrate risk scores with clinical features, resulting in a nomogram capable of predicting patient survival probabilities. This study introduces a novel prognostic risk model for HCC patients, aimed at stratifying patients by risk, enhancing personalized treatment strategies, and offering new insights into the role of T cell-related genes in HCC progression.