Comprehensive analysis of immune-related prognostic genes in the tumour microenvironment of hepatocellular carcinoma

Weike Gao,Siyao Liu,Luan Li,Dongliang Wang,Caiyun Liu,Peiming Guo,Dongsheng Zhang,Erhong Meng,Guanying Yu,Chengzhen Li,Shuai Hong,Lei Zhang,Guangjun Shi,Xinyin Han

doi:10.1186/s12885-021-08052-8

Abstract

BackgroundThe mortality rate of hepatocellular carcinoma (HCC) remains high worldwide despite surgery and chemotherapy. Immunotherapy is a promising treatment for the rapidly expanding HCC spectrum. Therefore, it is necessary to further explore the immune-related characteristics of the tumour microenvironment (TME), which plays a vital role in tumour initiation and progression.MethodsIn this research, 866 immune-related differentially expressed genes (DEGs) were identified by integrating the DEGs of samples from The Cancer Genome Atlas (TCGA)-HCC dataset and the immune-related genes from databases (InnateDB; ImmPort). Afterwards, 144 candidate prognostic genes were defined through weighted gene co-expression network analysis (WGCNA).ResultsSeven immune-related prognostic DEGs were identified using the L1-penalized least absolute shrinkage and selection operator (LASSO) Cox proportional hazards (PH) model, and the ImmuneRiskScore model was constructed on this basis. The prognostic index of the ImmuneRiskScore model was then validated in the relevant dataset. Patients were divided into high- and low-risk groups according to the ImmuneRiskScore. Differences in the immune cell infiltration of patients with different ImmuneRiskScore values were clarified, and the correlation of immune cell infiltration with immunotherapy biomarkers was further explored.ConclusionThe ImmuneRiskScore of HCC could be a prognostic marker and can reflect the immune characteristics of the TME. Furthermore, it provides a potential biomarker for predicting the response to immunotherapy in HCC patients.

Highlights

The mortality rate of hepatocellular carcinoma (HCC) remains high worldwide despite surgery and chemotherapy
Construction of a prognostic gene signature with the least absolute shrinkage and selection operator (LASSO) Cox proportional hazards (PH) model We revealed that 108 of the 144 immune hub genes were significantly associated with overall survival (OS) through univariate Cox regression analysis (Table S9)
The results demonstrate that the changes in the proportions of immune cells may be indirectly associated with the OS of HCC patients

Summary

Introduction

The mortality rate of hepatocellular carcinoma (HCC) remains high worldwide despite surgery and chemotherapy. HCC is the main type of primary liver cancer, and its increasing mortality rate is receiving growing concern Conventional treatments such as radiotherapy and chemotherapy do not significantly prolong overall survival (OS) in HCC patients [6]. Immunotherapy with immune checkpoint inhibitors (ICIs) is an important treatment option. These therapies are revolutionizing the clinical treatment pattern of multiple tumours, most notably advanced melanoma [7,8,9,10,11,12,13], non-small-cell lung cancer [14, 15] and renal cell carcinoma (RCC) [16, 17]. There is an urgent need for new, immune-based biomarkers to identify HCC patients who may have better prognoses after immunotherapy

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