Abstract

BACKGROUND: The tumor microenvironment is largely orchestrated by the immune cells. Considerable evidence has shown their excellent clinicopathological application value in assessment of clinical outcomes and immunotherapy efficacy. Hence, a moderate, individualized prognostic signature based on immune cells that can estimate prognosis and reflect the immune microenvironment in hepatocellular carcinoma (HCC) patients is greatly needed.

MATERIAL AND METHODS: Here, we systematically analyzed the expression differences and survival prediction value of tumor infiltrating immune cells by analyzing 638 HCC patients from 3 public cohorts, including 2 microarray datasets and 1 RNA sequencing dataset. CIBERSORT software, a computational algorithm, was used to calculate the relative levels of immune cells. Three immune microenvironment subtypes were defined via ConsensuClusterPlus package. Univariate and multivariate survival analyses were used to develop an individualized immune prognostic index based on immune cell pairs.

RESULTS: Notably, HCC patients with higher immune signatures score, utterly appreciable, suffered inferior prognosis (hazard ratio=2.742; 95% confidence interval: 1.887–3.983; P<0.001). Subgroup analysis suggested that the prognostic signature did particularly well in early-stage patients. Furthermore, moderate survival prediction value was also confirmed in another two independent cohorts GSE14520 and GSE76427.

CONCLUSIONS: This study provides a systematic view of the immune cells characteristics in HCC and suggests their superior survival monitoring performance.

Keywords: Allergy and Immunology, Carcinoma, Hepatocellular, Cellular Microenvironment, Prognosis, B-Lymphocyte Subsets, B-Lymphocytes, Cluster Analysis, Cohort Studies, Databases, Factual, Dendritic Cells, Eosinophils, Immune System, Killer Cells, Natural, Liver Neoplasms, Lymphocytes, Tumor-Infiltrating, Macrophages, Mast Cells, Monocytes, Multivariate Analysis, Neutrophils, Plasma Cells, Survival Rate, T-Lymphocyte Subsets, T-Lymphocytes, tumor microenvironment