Highly expressed centromere protein L indicates adverse survival and associates with immune infiltration in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a common cancer with poor prognosis. Due to the lack of effective biomarkers and its complex immune microenvironment, the effects of current HCC therapies are not ideal. In this study, we used the GSE57957 microarray data from Gene Expression Omnibus database to construct a co-expression network. The weighted gene co-expression network analysis and CIBERSORT algorithm, which quantifies cellular composition of immune cells, were used to identify modules related to immune cells. Four hub genes (EFTUD2, GAPDH, NOP56, PA2G4) were identified by co-expression network and protein-protein interactions network analysis. We examined these genes in TCGA database, and found that the four hub genes were highly expressed in tumor tissues in multiple HCC groups, and the expression levels were significantly correlated with patient survival time, pathological stage and tumor progression. On the other hand, methylation analysis showed that the up-regulation of EFTUD2, GAPDH, NOP56 might be due to the hypomethylation status of their promoters. Next, we investigated the correlations between the expression levels of four hub genes and tumor immune infiltration using Tumor Immune Estimation Resource (TIMER). Gene set variation analysis suggested that the four hub genes were associated with numerous pathways that affect tumor progression or immune microenvironment. Overall, our results showed that the four hub genes were closely related to tumor prognosis, and may serve as targets for treatment and diagnosis of HCC. In addition, the associations between these genes and immune infiltration enhanced our understanding of tumor immune environment and provided new directions for the development of drugs and the monitoring of tumor immune status.

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CDCA3 Is a Novel Prognostic Biomarker Associated with Immune Infiltration in Hepatocellular Carcinoma

BioMed Research International ◽

10.1155/2021/6622437 ◽

2021 ◽

Vol 2021 ◽

pp. 1-19

Author(s):

Zhihuai Wang ◽

Shuai Chen ◽

Gaochao Wang ◽

Sun Li ◽

Xihu Qin

Keyword(s):

Hepatocellular Carcinoma ◽

T Cells ◽

Immune Cell ◽

Disease Free Survival ◽

In Silico Analysis ◽

Gene Markers ◽

Free Survival ◽

Immune Infiltration ◽

Normal Tissues ◽

Tumor Tissues

Cell division cycle-associated protein-3 (CDCA3) contributes to the regulation of the cell cycle. CDCA3 plays an important role in the carcinogenesis of various cancers; however, the association between CDCA3 expression, prognosis of patients, and immune infiltration in the tumor microenvironment is still unknown. Here, we demonstrated that CDCA3 was differentially expressed between the tumor tissues and corresponding normal tissues using in silico analysis in the ONCOMINE and Tumor Immune Estimation Resource (TIMER) databases. We analyzed the relationship between the expression of CDCA3 and prognosis of patients with hepatocellular carcinoma (HCC) using the Kaplan–Meier plotter database and Gene Expression Profiling Interactive Analysis (GEPIA). Furthermore, we determined the prognostic value of CDCA3 expression using univariate and multivariate analyses. We observed that CDCA3 expression closely correlated with immune infiltration and gene markers of infiltrating immune cells in the TIMER database. CDCA3 was highly expressed in the tumor tissues than in the adjacent normal tissues in various cancers, including HCC. Increased expression of CDCA3 was accompanied by poorer overall survival (OS), relapse-free survival (RFS), progression-free survival (PFS), and disease-specific survival (DSS). The correlation between CDCA3 expression and OS and disease-free survival (DFS) was also studied using GEPIA. CDCA3 expression was associated with the levels of immune cell infiltration and was positively correlated with tumor purity. Moreover, CDCA3 expression was associated with gene markers such as PD-1, CTLA4, LAG3, and TIM-3 from exhausted T cells, CD3D, CD3E, and CD2 from T cells, and TGFB1 and CCR8 located on the surface of Tregs. Thus, we demonstrated that CDCA3 may be a potential target and biomarker for the management and diagnosis of HCC.

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WGCNA and LASSO algorithm constructed an immune infiltration-related 5-gene signature and nomogram to improve prognosis prediction of hepatocellular carcinoma

BIOCELL ◽

10.32604/biocell.2022.016989 ◽

2022 ◽

Vol 46 (2) ◽

pp. 401-415

Author(s):

MENG FANG ◽

JING GUO ◽

HAIPING WANG ◽

ZICHANG YANG ◽

HAN ZHAO ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Gene Signature ◽

Immune Infiltration ◽

Prognosis Prediction

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Decreased Expression of KPNA2 in Hepatocellular Carcinoma Infers Favorable Prognosis and High Immune Infiltrating Level

10.21203/rs.3.rs-691618/v1 ◽

2021 ◽

Author(s):

kangming zhu ◽

yvndi zhang ◽

hui yvan ◽

jing li

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Logistic Regression ◽

Survival Rate ◽

Western Blotting ◽

Good Prognosis ◽

Overall Survival Rate ◽

Pathological Stage ◽

Down Regulation ◽

Immune Infiltration

Abstract BackgroundLiver hepatocellular carcinoma (LIHC) is an important pathological type of liver cancer. The immune infiltration of the tumor microenvironment is negatively correlated with the overall survival rate of LIHC. At present , the role and molecular mechanism of KPNA2 in LIHC have not been elucidated, and the prognostic correlation between the two and the immune infiltration of LIHC are still unclear. Our study evaluated the role of KPNA2 in LIHC through TCGA data.MethodGene expression profiling interactive analysis (GEPIA) is used to analyze the expression of KPNA2 in LIHC. We evaluated the impact of KPNA2 on the survival of LIHC patients through the survival module. Then, We downloaded the LIHC data set from TCGA. Logistic regression was used to analyze the correlation between clinical information and KPNA2 expression. Cox regression analysis was used to analyze the clinicopathological characteristics related to the overall survival rate of TCGA patients. In addition, we used the "correlation" modules of CIBERSORT and GEPIA to explore the correlation between KPNA2 and cancer immune infiltrate. Western blotting was used to detect the expression of KPNA2.ResultUsing logistic regression for univariate analysis, increased KPNA2 expression was significantly correlated with pathological stage, tumor status, and lymph node status. In addition, multivariate analysis showed that down-regulation of KPNA2 expression, negative pathological stage and distant metastasis are independent prognostic factors for good prognosis. Specifically, CIBERSORT analysis was used to establish a negative correlation between the up-regulated expression of KPNA2 and the level of immune infiltration of B cells, NK cells, mast cells, and T cells. In addition, we confirmed this in the "Association" module of GEPIA. The expression of KPNA2 in LIHC tissues was significantly lower than that in adjacent normal tissues by western blotting.ConclusionThe down-regulation of KPNA2 expression is associated with a good prognosis and an increase in the proportion of immune cells in LIHC. These conclusions indicate that KPNA2 is related to the level of immune infiltration of LIHC and can be used as a potential prognostic biomarker of LIHC and a potential target for clinical tumor treatment.

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Identification of CDC20 As an Immune Infiltration-Correlated Prognostic Biomarker in Hepatocellular Carcinoma

10.21203/rs.3.rs-400598/v1 ◽

2021 ◽

Author(s):

Chen Xiong ◽

Zhihuai Wang ◽

Guifu Wang ◽

Chi Zhang ◽

Shengjie Jin ◽

...

Keyword(s):

Gene Expression ◽

Hepatocellular Carcinoma ◽

T Cells ◽

Poor Prognosis ◽

Prognostic Value ◽

Cox Regression ◽

Cancer Genome ◽

Regression Analyses ◽

Ubiquitin Protein Ligase ◽

Immune Infiltration

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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SLC39A10 Upregulation Predicts Poor Prognosis, Promotes Proliferation and Migration, and Correlates with Immune Infiltration in Hepatocellular Carcinoma

Journal of Hepatocellular Carcinoma ◽

10.2147/jhc.s320326 ◽

2021 ◽

Vol Volume 8 ◽

pp. 899-912

Author(s):

Zuyi Ma ◽

Zhenchong Li ◽

Shujie Wang ◽

Qi Zhou ◽

Zuguang Ma ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Poor Prognosis ◽

Immune Infiltration ◽

And Migration ◽

Proliferation And Migration

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Nuclear Respiratory Factor 1 Associated with Prognosis and Immune Infiltration in Hepatocellular Carcinoma

10.21203/rs.3.rs-52843/v1 ◽

2020 ◽

Author(s):

Dan Wang ◽

Linlin Huang ◽

Xiaojing Zhang ◽

Pingping Sun ◽

Yapeng Lu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

T Cells ◽

Chronic Hepatitis ◽

Mrna Expression ◽

Tumor Infiltrating Lymphocytes ◽

Cox Regression Analysis ◽

Nuclear Respiratory Factor ◽

Immune Infiltration ◽

Nuclear Respiratory Factor 1 ◽

Infiltrating Lymphocytes

Abstract Background: Recent studies have shown that functional mitochondria are essential for cancer cells. Nuclear respiratory factor 1 (NRF1) is a transcription factor that activates mitochondrial biogenesis and the expression of the respiratory chain, but little is known about its prognostic value and tumor-infiltrating lymphocytes association. Here, we evaluated the association among expression of NRF1, clinicopathological characteristics, survival and immune infiltration in hepatocellular carcinoma (HCC).Methods: We used the Tumor Immune Estimation Resource (TIMER) to analyze the difference of NRF1 mRNA expression in human cancers. Clinical-pathological information and follow-up data were collected from HCC (n = 171) and chronic hepatitis (n = 113) patients. NRF1 expression were scored based on the percentage and intensity of immunohistochemical staining in pathological slides. Correlations between clinical features and the expression of NRF1 were evaluated by Chi-square test, Kaplan-Meier curves, logrank tests and multivariate Cox regression analysis. The correlations between NRF1 expression and gene marker sets of tumor infiltrating lymphocytes (TILs) were analyzed by TIMER and Gene Expression Profiling Interactive Analysis (GEPIA) databases. Results: NRF1 mRNA expression was significantly higher in HCC than in normal tissue. Compared with chronic hepatitis, more frequency of NRF1 high expression are found in HCC (31.58 % vs 13.27 %, P < 0.001, P < 0.001). In addition, the NRF1 expression was significantly associated with hepatic cirrhosis (P = 0.021) and vascular invasion (P = 0.025). NRF1 expression was also a significant independent predictor of survival in HCC (P = 0.003; HRadj = 0.20; 95% CI = 0.09 – 0.44). NRF1 showed positively correlated with TILs, including B cell (r = 0.384, P = 1.68e-13), CD8+ T cells (r = 0.246, P = 3.99e-06), CD4+ T cells (r = 0.535, P = 6.90e-27), macrophage (r = 0.506, P = 1.52e-23), neutrophils (r = 0.465, P = 6.08e-20) and dendritic cell (r = 0.404, P = 8.61e-15). The marker genes of TILs correlated significantly with NRF1 expression.Conclusions: NRF1 expression was a useful independent prognostic factor and correlated with tumor immune infiltration in HCC.

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