CXCL5 Has Potential to Be a Marker for Hepatocellular Carcinoma Prognosis and Was Correlating With Immune Infiltrates.

Yuan Nie,Qi Liu,Xuan Zhu,Mei-Chun Jiang,Cong Liu

doi:10.3389/fonc.2021.637023

Abstract

BackgroundsTumor microenvironment (TME) plays a crucial role in the initiation and progression of Hepatocellular Carcinoma (HCC), especially immune infiltrates. However, there is still a challenge in understanding the modulation of the immune and stromal components in TME, especially TME related genes.MethodsThe proportion of tumor-infiltrating immune cells (TICs) and the immune and stromal scores in 374 HCC patients from The Cancer Genome Atlas (TCGA) database were determined using CIBERSORT and ESTIMATE computational methods. The final screened genes were confirmed by the PPI network and univariate Cox regression of the differentially expressed genes based on different immune or stromal scores. The correlation between the expression levels of the final gene interactions and the clinical characteristics was based on TCGA database and local hospital data. Gene set enrichment analysis (GSEA) and the effect of CXCL5 expression on TICs were conducted.ResultsThere were correlations between the expression of CXCL5 and survival of HCC patients and TMN classification both in TCGA database and local hospital data. The immune-related activities were enriched in the high-expression group; however, the metabolic pathways were enriched in the low-expression group. The result of CIBERSORT analyzing had indicated that CXCL5 expression were correlated with the proportion of NK cells activated, macrophages M0, Mast cells resting, Neutrophils.ConclusionsCXCL5 was a potential prognostic marker for HCC and provides clues regarding immune infiltrates, which offers extra insight for therapeutics of HCC, however, more independent cohorts and functional experiments of CXCL5 are warranted.

Highlights

Liver cancer is a typical inflammation driven tumor and often develops from chronic hepatitis and cirrhosis [1]
Previous studies showed that the tumor-infiltrating immune cells (TICs) in tumor microenvironment (TME) plays an important role in development of Hepatocellular carcinoma (HCC) and served as a predicting parameter for prognosis
The transcriptome RNA-seq data of 424 cases were downloaded from The Cancer Genome Atlas (TCGA) database followed by calculating with CIBERSORT and ESTIMATE algorithms

Summary

Introduction

Liver cancer is a typical inflammation driven tumor and often develops from chronic hepatitis and cirrhosis [1]. Increasing evidence demonstrated the importance of the tumor microenvironment (TME) in the tumor development, especially in HCC [4]. The immunosuppressive microenvironment of HCC can promote immune tolerance through a variety of mechanisms. Immunotherapy that activates tumor specific immune response brings new hope for the treatment of HCC. The microenvironment of HCC is mainly composed of tumor associated macrophages, tumor associated neutrophils and myeloid-derived suppressor cells (MDSCs), tumor associated fibroblasts, tumor infiltrating lymphocytes and other cellular components, as well as extracellular matrix, cytokines, and other non-cellular components. Previous studies showed that the tumor-infiltrating immune cells (TICs) in TME plays an important role in development of HCC and served as a predicting parameter for prognosis. Immune cells in tumor microenvironment together with cancer cells and extracellular matrix, inhibiting the antitumor activity of immune cells and playing an important role in promoting of HCC. The analysis of TICs of HCC is helpful to study the pathogenesis of HCC

Methods

Results

Conclusion