Prediction of Hepatocellular Carcinoma Prognosis and Immune Cell Infiltration Using Gene Signature Associated with Inflammatory Response.

Bin-Bin Da,Shuai Luo,Yin-Shan Yang,Yao Xiao,Ming Huang,Hai-Lei Wang,Fei Song,Yang Fu,Rong Ding,Osamah Ibrahim Khalaf

doi:10.1155/2022/2415129

Abstract

It has been demonstrated that the inflammatory response influences cancer development and can be used as a prognostic biomarker in various tumors. However, the relevance of genes associated with inflammatory responses in hepatocellular carcinoma (HCC) remains unknown. The Cancer Genome Atlas (TCGA) database was analyzed using weighted gene coexpression network analysis (WGCNA) and differential analysis to discover essential inflammatory response-related genes (IFRGs). Cox regression studies, both univariate and multivariate, were employed to develop a prognostic IFRGs signature. Additionally, Gene Set Enrichment Analysis (GSEA) was used to deduce the biological function of the IFRGs signature. Finally, we estimated immune cell infiltration using a single sample GSEA (ssGSEA) and x-cell. Our results revealed that, among the major HCC IFRGs, two (DNASE1L3 and KLKB1) were employed to create a predictive IFRG signature. The IFRG signature could correctly predict overall survival (O.S) as per Kaplan-Meier time-dependent roc curves analysis. It was also linked to pathological tumor stage and T stage and might be used as a prognostic predictor in HCC. GSEA analysis concluded that the IFRG signature might influence the immune response in HCC. Immunological cell infiltration and immune checkpoint molecule expression differed in the high-risk and low-risk groups. As a result of our findings, DNASILE may play a role in the tumor microenvironment. However, more research is necessary to confirm the role of DNASE1L3 and KLKB1.

Highlights

Hepatocellular carcinoma (HCC) is the most frequent subtype of malignant hepatic cancer globally, accounting for 90% of all cases [1]
The MEmidnightblue module was defined as an HCC-related module, and 133 genes in the MEmidnightblue module were defined as HCC-related genes
The inflammatory response-related genes (IFRGs) signature was associated with pathological tumor stage and pathological T stage, implying that it could be used as an independent prognostic predictor in HCC

Summary

Introduction

Hepatocellular carcinoma (HCC) is the most frequent subtype of malignant hepatic cancer globally, accounting for 90% of all cases [1]. HCC is the 5th most frequent malignancy and the 3rd most significant cause of cancer-related death worldwide [2, 3]. It has been suggested that hepatitis B and hepatitis C virus infection, alcohol abuse, and aflatoxin exposure are usually associated with HCC occurrence [4, 5]. The rapid development of gene sequencing technology offers some opportunities to unravel the molecular mechanisms of cancer [8, 9]. Resulting in that utilizing sequencing technology to screen the prognostic biomarkers and therapeutic targets of cancers has become prevalent. The molecular mechanism of HCC occurrence and progression remains a challenge

Methods

Results

Discussion

Conclusion