Identification of CDC20 as an immune infiltration-correlated prognostic biomarker in hepatocellular carcinoma.

Guoqing Jiang,Chi Zhang,Zhihuai Wang,Guifu Wang,Chen Xiong,Shengjie Jin,Dousheng Bai

doi:10.1007/s10637-021-01126-1

Guoqing Jiang, Chi Zhang + Show 5 more

Open Access

https://doi.org/10.1007/s10637-021-01126-1

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Abstract

Hepatocellular carcinoma (HCC) is a malignancy with a poor prognosis. E3 ubiquitin-protein ligases play essential roles in HCC, such as regulating progression, migration, and metastasis. We aimed to explore a hub E3 ubiquitin-protein ligase gene and verify its association with prognosis and immune cell infiltration in HCC. Cell division cycle 20 (CDC20) was identified as a hub E3 ubiquitin-protein ligase in HCC by determining the intersecting genes in a protein-protein interaction (PPI) network of differentially expressed genes (DEGs) using HCC data from the International Cancer Genome Consortium (ICGC) and the gene list of 919 E3 ubiquitin-protein ligases. DEGs and their correlations with clinicopathological features were explored in The Cancer Genome Atlas (TCGA), ICGC, and Gene Expression Omnibus (GEO) databases via the Wilcoxon signed-rank test. The prognostic value of CDC20 was illustrated by Kaplan-Meier (K-M) curves and Cox regression analyses. Subsequently, the correlation between CDC20 and immune infiltration was demonstrated via the Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA). CDC20 expression was significantly higher in HCC than in normal tissues (all P < 0.05). High CDC20 expression predicted a poor prognosis and might be an independent risk factor in HCC (P < 0.05). Additionally, CDC20 was correlated with the immune infiltration of CD8 + T cells, T cells (general), monocytes, and exhausted T cells. This study reveals the potential prognostic value of CDC20 in HCC and demonstrates that CDC20 may be an immune-associated therapeutic target in HCC because of its correlation with immune infiltration.

Highlights

Hepatocellular carcinoma (HCC) is the sixth most common primary tumour and the fourth leading cause of cancer-related death worldwide[1]
We identified cell division cycle 20 (CDC20) as a hub E3 ubiquitin-protein ligase in HCC by determining the intersecting genes in a protein-protein interaction (PPI) network of differentially expressed genes (DEGs) in HCC data from the International Cancer Genome Consortium (ICGC) and 919 E3 ubiquitin-protein ligase genes from the Integrated annotations for Ubiquitin and Ubiquitin-like Conjugation Database (IUUCD)
The expression level of CDC20 was higher in HCC samples than in normal samples To analyse the differential expression of CDC20 between HCC and normal samples, expression data from the The Cancer Genome Atlas (TCGA), ICGC, and Gene Expression Omnibus (GEO) databases were analysed

Summary

Introduction

Hepatocellular carcinoma (HCC) is the sixth most common primary tumour and the fourth leading cause of cancer-related death worldwide[1]. Due to the characteristics of invasion, metastasis, and immune escape, though many advances have improved the treatment of HCC, its prognosis remains dismal[3, 4]. It is necessary to explore the relevant mechanism of HCC progression and identify novel therapeutic targets to improve the prognosis of HCC. As an increasing number of E3 ubiquitin-protein ligases have been discovered to play oncogenic or anti-oncogenic roles in cancers, the important roles of E3 ubiquitinprotein ligases in the development and carcinogenesis of malignancies have been illustrated. Some E3 ubiquitin ligases are correlated with chemoresistance and may be potential cancer treatment targets[6, 7]. It is of great significance to explore hub E3 ubiquitin-protein ligases in HCC to identify new biomarkers and treatment targets

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