Integrated analysis of single-cell and bulk RNA-sequencing identifies a signature based on NK cell marker genes to predict prognosis and immunotherapy response in hepatocellular carcinoma

Abstract

Background: Prognostic modeling of NK cell marker genes in patients with hepatocellular carcinoma based on single cell sequencing and transcriptome data analysis.

Methods: Marker genes of NK cells were analyzed according to single cell sequencing data of hepatocellular carcinoma. Univariate Cox regression, lasso regression analysis, and multivariate Cox regression were performed to estimate the prognostic value of NK cell marker genes. TCGA, GEO and ICGC transcriptomic data were applied to build and validate the model. Patients were divided into high and low risk groups based on the median risk score. XCELL, timer, quantitative sequences, MCP counter, EPIC, CIBERSORT and CIBERSORT-abs were performed to explore the relationship between risk score and tumor microenvironment in hepatocellular carcinoma. Finally the sensitivity of the model to chemotherapeutic agents was predicted.

Results: Single-cell sequencing identified 207 marker genes for NK cells in hepatocellular carcinoma. Enrichment analysis suggested that NK cell marker genes were mainly involved in cellular immune function. Eight genes were selected for prognostic modeling after multifactorial COX regression analysis. The model was validated in GEO and ICGC data. Immune cell infiltration and function were higher in the low-risk group than in the high-risk group. The low-risk group was more suitable for ICI and PD-1 therapy. Half-maximal inhibitory concentrations of Sorafenib, Lapatinib, Dabrafenib, and Axitinib were significantly different on the two risk groups.

Conclusion: A new signature of hepatocyte NK cell marker genes possesses a powerful ability to predict prognosis and immunotherapeutic response in patients with hepatocellular carcinoma.

Keywords: Hepatocellular carcinoma; Immunotherapy; NK cell marker genes; Single-cell RNA-sequencing.