Expression, immune infiltration and clinical significance of SPAG5 in hepatocellular carcinoma: A gene expression‐based study

Abstract Hepatocellular carcinoma (HCC) is a malignancy with a poor prognosis. Some E3 ubiquitin-protein ligases play essential roles in HCC development. We aimed to explore a hub E3 ubiquitin-protein ligase gene and verify its association with prognosis and immune cell infiltration in HCC. 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). 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). K-M curves and Cox regression analyses showed that high CDC20 expression predicted a poor prognosis and might be an independent risk factor for HCC prognosis (P < 0.05). Additionally, the TIMER and GEPIA results indicated that CDC20 is correlated with the immune infiltration of CD8 + T cells, T cells (general), monocytes, and exhausted T cells. This research revealed the potential prognostic value of CDC20 in HCC and demonstrated that CDC20 might be an immune-associated therapeutic target in HCC because of its correlation with immune infiltration.

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RNA N6-Methyladenosine Patterns in Hepatocellular Carcinoma Reveal a Distinct Immune Infiltration Landscape and Clinical Significance

Medical Science Monitor ◽

10.12659/msm.930994 ◽

2021 ◽

Vol 27 ◽

Author(s):

Hua Zhao ◽

Qiujun Zhou ◽

Chengwei Shi ◽

Yaojian Shao ◽

Junjie Ni ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Clinical Significance ◽

Immune Infiltration

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Gene Risk Signature of m6A Regulators, KIAA1429, YTHDF1, YTHDF2, METTL3 and Its Relationship with Immune Infiltration in Hepatocellular Carcinoma

10.21203/rs.3.rs-47948/v1 ◽

2020 ◽

Author(s):

Jingjing Guo ◽

Liwei Wang ◽

Hanfeng Xu ◽

Chuandong Zhu ◽

Jianning Wang ◽

...

Keyword(s):

Gene Expression ◽

Hepatocellular Carcinoma ◽

Cox Regression ◽

Clinical Information ◽

High Risk Group ◽

Consensus Clustering ◽

Immune Infiltration ◽

Infiltrating Cells ◽

Cancer Tissues ◽

The Relationship

Abstract Background: Hepatocellular carcinoma (HCC) is a tumor of the digestive system with high mortality. N6-methyladenosine (m6A) is one of the most common forms of mRNA modification. Tumor neoantigens play an important role in anti-tumor immune response and predict the clinical response of immunotherapy. There are few studies on the relationship between m6A regulators and immune infiltrating cells. The objective of this study was to determine the gene expression and prognostic value of m6A regulators in hepatocellular carcinoma. Further, we explored the relationship between m6A regulators and immune-infiltrating cells.Methods: 13 m6A regulators expressions in 374 cancer tissues and 50 normal tissues were analyzed using RNA-seq data and clinical information in the TCGA database. Survival package was used to analyze the survival of patients in the two groups, and the corresponding clinical characteristics and gene expression were analyzed using univariate and multivariate Cox regression. We evaluated the expression of KIAA1429, YTHDF1, YTHDF2, and METTL3 in HCC and its correlation with TIICs using TIMER and CIBERSORT.Results: Most m6A regulators had higher expression levels in 374 cancer tissues. We confirmed two groups of HCC patients using a consensus clustering method. The prognosis of the cluster 1 group was poor compared with that of the cluster 2 group. The m6A regulators, KIAA1429, YTHDF1, YTHDF2, and METTL3 are highly expressed in the high-risk group of HCC. Furthermore, it was found that four m6A regulators (KIAA1429, YTHDF1, YTHDF2, and METTL3) are closely related to the clinicopathological characteristics and poor prognostic marker of hepatocellular carcinoma. We analyzed the correlation between KIAA1429, YTHDF1, YTHDF2, and METTL3 expression and the level of immune invasion of HCC.Conclusion: KIAA1429, YTHDF1, YTHDF2, and METTL3 as m6A regulators may regulate the tumor microenvironment through tumor immune infiltration cells to exert immune anti-tumor effects. KIAA1429, YTHDF1, YTHDF2, and METTL3 as molecular markers providing a new target for therapy of HCC in the further.

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