An immunogenomic signature for molecular classification in hepatocellular carcinoma

Weiwei Zhuang,Hongwei Sun,Shanshan Zhang,Yilin Zhou,Wanqing Weng,Boda Wu,Tingbo Ye,Weiguo Huang,Zhuo Lin,Liang Shi,Keqing Shi

doi:10.1016/j.omtn.2021.06.024

Abstract

Immunity plays an important role in tumor development. In this study, we aimed to investigate molecular classification and its prognostic value in hepatocellular carcinoma (HCC) based on immune signature. Gene set enrichment analysis (GSEA) was used to calculate scores of immune pathways for HCC and hierarchical clustering in two databases (The Cancer Genome Atlas [TCGA], Liver Cancer-RIKEN, JP [LIRI_JP]). The scores of the immune microenvironment and the proportions of 22 immune cells were also calculated. Single-sample GSEA (ssGSEA) was used to screen survival prognosis-related immune pathways and calculate the hazard radio of differentially expressed immune-related genes (IRGs), which were validated in clinical samples and multiple datasets. Based on the immune characteristics, we identified three HCC subtypes, namely immunity high (Immunity_H), immunity medium (Immunity_M), and immunity low (Immunity_L), and confirmed that the classification was reliable and predictable. Immunity_H with a higher immune and stromal score indicated better survival rate. Cox regression analysis showed that IL18RAP and IL7R were the protective genes. Immune risk score was the independent risk factor of overall survival in HCC patients. These results indicated that immunogenomic classification could distinguish HCC patients with different immune status, which could impact the prognosis of the patients with HCC.

Highlights

Hepatocellular carcinoma (HCC) is a common cancer worldwide with a high mortality rate.[1,2] The pathogenesis of HCC is a complex process, which is influenced by multiple factors, such as environmental factors and the individual’s own genes.[3]
Immunity_M < Immunity_L) (Kruskal-Wallis test, p < 0.001) (Figures 3C and 3F). These results indicated that the largest number of immune cells and stromal cells was found in Immunity_H, and Immunity_L contained the largest number of tumor cells
The expression levels of IL7R and IL18RAP in surviving individuals were higher than those in dead individuals (Figure S2). These results demonstrated that IL7R and IL18RAP were downregulated in HCC patients on mRNA, implying the importance of IL7R and IL18RAP in HCC pathogens

Summary

Introduction

Hepatocellular carcinoma (HCC) is a common cancer worldwide with a high mortality rate.[1,2] The pathogenesis of HCC is a complex process, which is influenced by multiple factors, such as environmental factors and the individual’s own genes.[3] A large number of previous studies have indicated that the immune microenvironment of the primary tumor is an important prognostic factor.[4] effective diagnostic indicators of the immune microenvironment are still lacking, resulting in fuzzy prognosis accuracy in HCC. The conventional treatments of HCC include surgery, chemotherapy, and radiotherapy,[5,6] which have a better curative effect in the early stages of cancer. It is urgent to find biomarkers for early detection and prognostic evaluation of HCC.[2]

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Conclusion