Construction of CD8+ T cell-associated risk signature in hepatocellular carcinoma based on single-cell RNA-seq and bulk RNA-seq data

Abstract Background Hepatocellular carcinoma (HCC) is the most prevalent form of primary liver cancer, characterized by high recurrence and mortality rates. Specific CD8 + T cells have a central role in pathogenesis of HCC by recognizing and destroying tumor cells. Method Common CD8 + T cell signatures were obtained from bulk RNA-seq and scRNA-seq analysis. Univariate Cox regression, LASSO regression, and Multivariate Cox regression was sequentially utilized on the CD8 + T cell signatures to establish a risk scoring model. Prognostic value of the model was verified in the external datasets GSE14520. Immune analysis and Drug Sensitivity analysis was performed in high risk and low risk group. Immunohistochemistry (IHC) was employed to ascertain the expression of model genes in 10 HCC samples and corresponding adjacent tissues. Result A three-gene risk scoring model ( KLRB1 , RGS2 and TNFRSF1B ) was constructed from CD8 + T cell common signatures. In terms of immune cell infiltration, low-risk group demonstrated higher abundance of CD8 + T cells, and M1 Macrophages., whereas high-risk group demonstrated higher abundance of M2 Macrophages and resting mast cells. As for immunotherapy, patients in high-risk group may not respond well. BMS-754807, Gemcitabine, et al exhibited sensitive to patients in low-risk group, AZD6482 and SB505124 may serve as novel potential targeted drugs for patients in high-risk group. In comparison to normal tissues, KLRB1 , RGS2 , and TNFRSF1B exhibited a reduced expression level, confirming our findings in publicly available databases. Conclusion In conclusion, we constructed a CD8 + T cell-associated risk scoring model consisting of KLRB1 , RGS2 and TNFRSF1B to predict prognosis and provide potential drugs for HCC treatment.