Constructing an immune-related prognostic signature for predicting prognosis and immune response in hepatocellular
Lichao Cao1, Deliang Huang2, Shenrui Zhang1
1Shenzhen Nucleus Gene Technology Co., Ltd., 518071, Shenzhen, Guangdong Province, China.
Background:
Currently, there are few studies on immune-related prognostic analysis of hepatocellular carcinoma (HCC). Our aim was to establish an immune-correlated prognostic model for HCC.
Methods:
Immune-associated cells were obtained from the scRNA-seq dataset (GSE149614) of HCC. Differentially expressed genes between normal and tumor cells from immune-associated cells and the immune-related genes from the ImmPort database were used to identify immune-related differentially expressed genes (IRDEGs). Subsequently, the risk model was established in the TCGA-LIHC cohort (n = 438) from the Cancer Genome Atlas (TCGA) database by using Kaplan-Meier (K-M) survival curve, univariate/multivariate Cox regression analysis. Subsequently, we further analyzed tumor immune microenvironment characteristics, somatic mutation, immune checkpoint and its ligand expression levels between high- and low-risk groups, as well as drug sensitivity prediction. ICGC cohort was set as the validation cohort. TCGA-LIHC cohort and three independent the Gene Expression Omnibus (GEO) datasets (GSE54236, GSE14520, and GSE64041) was used to verify IRDEGs expression, as well as PCR assays using clinical samples.
Results:
The IRDEGs was composed of 4 genes, namely B2M, SPP1, PPIA, and HRG. The 438 HCC patients were divided into high- and low-risk group. The high-risk group was associated with poor prognosis, including higher T stage, advanced pathological stages, less immune cell infiltration, higher TP53 mutation rate, the high expression of CTLA4 and HAVCR2. Besides, high-risk populations benefit from most chemotherapy drugs. Similarly, the performance of the risk model was validated in the ICGC. All four datasets (TCGA-LIHC cohort, GSE54236, GSE14520, and GSE64041) and clinical q-PCR results demonstrated that, compared with normal samples, the expressions of B2M and HRG were lower in tumor samples, and the expression of SPP1 was higher.
Conclusion:
In summary, the immune-related prognostic signature had a good predictive performance on prognosis and immunotherapy for HCC patients.
