Research Paper Volume 12, Issue 6 pp 5479—5499

Prognostic values of immune scores and immune microenvironment-related genes for hepatocellular carcinoma

Peng-lei Ge1, , Shi-fang Li1, , Wei-wei Wang2, , Chun-bo Li1, , Yu-bin Fu1, , Zheng-kai Feng1, , Lin Li1, , Gong Zhang1, , Zhi-qiang Gao1, , Xiao-wei Dang1, , Yang Wu1, ,

  • 1 Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
  • 2 Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China

Received: November 19, 2019       Accepted: February 5, 2020       Published: March 25, 2020
How to Cite

Copyright © 2020 Ge et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


It is crucial to grasp the characteristics of tumour immune microenvironment to improve effects of immunotherapy. In this study, the immune and stromal scores of 371 cases were calculated for quantitative analysis of immune and stromal cell infiltration in the tumour microenvironment of hepatocellular carcinoma (HCC). The weighted gene co-expression network analysis and protein–protein interaction network were analysed to identify immune microenvironment-related genes. The results showed that patients with high immune scores had a higher 4-year recurrence-free rate. TP53, CTNNB1, and AXIN1 mutations significantly varied with immune scores. In immune score-related modules analysis, Kyoto encyclopaedia of genes and genomes pathways and gene ontology terms were closely related to immune processes, tumorigenesis, and metastasis. Twelve new immune microenvironment-related genes were identified and had significantly positive correlations with seven immune checkpoint genes. In prognostic analysis, eleven immune microenvironment-related genes exhibited high expression, nine of which were validated in the GSE62232 dataset and were significantly associated with a good prognosis. Our findings suggest that calculating immune score and stromal score could help to determine tumour purity and immune cell infiltration in the tumour microenvironment. Nine immune microenvironment-related genes identified in this study had potential as prognostic markers for HCC.


HCC: Hepatocellular carcinoma; ESTIMATE: Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data; WGCNA: Weighted gene co-expression network analysis; PPI: Protein–protein interaction; KEGG: Kyoto encyclopaedia of genes and genomes; GO: Gene ontology; TCGA: The cancer genome atlas; FPKM: Fragments per kilobase million; SNP: Single nucleotide polymorphism; LCK: Lymphocyte-specific protein tyrosine kinase; GEO: Gene Expression Omnibus; qRT-PCR: Quantitative real-time polymerase chain reaction; IHC: Immunohistochemical; MAD: mean areal density.