scholarly journals EOGT Correlated With Immune Infiltration: A Candidate Prognostic Biomarker for Hepatocellular Carcinoma

2022 ◽  
Vol 12 ◽  
Author(s):  
Yang Shu ◽  
Lingling He ◽  
Meixin Gao ◽  
Fan Xiao ◽  
Junru Yang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Cox Regression ◽  
Tumor Staging ◽  
Suppressor Cells ◽  
Immunofluorescent Staining ◽  
Advanced Hepatocellular Carcinoma ◽  
Poor Overall Survival ◽  
Immune Infiltration ◽  
Advanced Tumor

BackgroundA preliminary study by our group revealed that the deficiency of EGF domain-specific O-linked N-acetylglucosamine transferase (EOGT) impaired regulatory T-cell differentiation in autoimmune hepatitis. Nevertheless, the prognostic value of EOGT in advanced hepatocellular carcinoma (HCC) and its relationship with immune infiltration remain obscured.MethodsInitially, EOGT expression was evaluated by Oncomine, TIMER, GEO, and UALCAN databases. Besides, the prognostic potential of EOGT expression was analyzed using GEPIA, Kaplan–Meier plotter, CPTAC, Cox regression, and nomogram in HCC samples. Furthermore, we investigated the association between EOGT expression and tumor mutation burden, DNA methylation, and immune infiltration in addition to its possible mechanism via cBioPortal, TIMER, GEPIA, ESTIMATE, CIBERSORT, GSEA, STRING, and Cytoscape.ResultsThe expression of EOGT in HCC was significantly higher than that in normal tissues. Additionally, elevated EOGT expression was correlated with advanced tumor staging and linked to poor overall survival and relapse-free survival, serving as a significant unfavorable prognostic indicator in HCC patients. Remarkably, our results revealed that high-EOGT expression subgroups with elevated TP53 or low CTNNB1 mutations have worse clinical outcomes than the others. Regarding immune infiltration, immunofluorescent staining showed that immune cells in HCC were positive for EOGT. Besides, elevated EOGT expression was linked to exhausted T cells and immune suppressor cells in HCC samples. More importantly, the proportion of CD8+ T cells was reduced in HCC samples with a high level of EOGT expression, but EOGT did not exhibit prognostic potential in HCC samples with increased CD8+ T cells.ConclusionsEOGT may hold great potential as a novel biomarker to distinguish prognosis and immune profiles of HCC patients.

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

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.

scholarly journals Construction and Validation of a Combined Ferroptosis and Hypoxia Prognostic Signature for Hepatocellular Carcinoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Kai Wen ◽  
Yongcong Yan ◽  
Juanyi Shi ◽  
Lei Hu ◽  
Weidong Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cox Regression ◽  
Tumor Staging ◽  
Tumor Therapy ◽  
Normal Liver ◽  
Cancer Genome ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Prognostic Signature ◽  
Advanced Tumor

Background: Ferroptosis, as a unique programmed cell death modality, has been found to be closely related to the occurrence and development of hepatocellular carcinoma (HCC). Hypoxia signaling pathway has been found to be extensively involved in the transformation and growth of HCC and to inhibit anti-tumor therapy through various approaches. However, there is no high-throughput study to explore the potential link between ferroptosis and hypoxia, as well as their combined effect on the prognosis of HCC.Methods: We included 370 patients in The Cancer Genome Atlas (TCGA) database and 231 patients in the International Cancer Genome Consortium (ICGC) database. Univariate COX regression and Least Absolute Shrinkage and Selection Operator approach were used to construct ferroptosis-related genes (FRGs) and hypoxia-related genes (HRGs) prognostic signature (FHPS). Kaplan–Meier method and Receiver Operating Characteristic curves were analyzed to evaluate the predictive capability of FHPS. CIBERSOR and single-sample Gene Set Enrichment Analysis were used to explore the connection between FHPS and tumor immune microenvironment. Immunohistochemical staining was used to compare the protein expression of prognostic FRGs and HRGs between normal liver tissue and HCC tissue. In addition, the nomogram was established to facilitate the clinical application of FHPS.Results: Ten FRGs and HRGs were used to establish the FHPS. We found consistent results in the TCGA training cohort, as well as in the independent ICGC validation cohort, that patients in the high-FHPS subgroup had advanced tumor staging, shorter survival time, and higher mortality. Moreover, patients in the high-FHPS subgroup showed ferroptosis suppressive, high hypoxia, and immunosuppression status. Finally, the nomogram showed a strong prognostic capability to predict overall survival (OS) for HCC patients.Conclusion: We developed a novel prognostic signature combining ferroptosis and hypoxia to predict OS, ferroptosis, hypoxia, and immune status, which provides a new idea for individualized treatment of HCC patients.

scholarly journals Identification of Prognostic Biomarkers and Correlation With Immune Infiltrates in Hepatocellular Carcinoma Based on a Competing Endogenous RNA Network

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhangya Pu ◽  
Yuanyuan Zhu ◽  
Xiaofang Wang ◽  
Yun Zhong ◽  
Fang Peng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Survival Analysis ◽  
Immune Cell ◽  
Cox Regression ◽  
Quantitative Polymerase Chain Reaction ◽  
Prognostic Biomarkers ◽  
Hub Genes ◽  
Immune Infiltration ◽  
Cerna Network

BackgroundHepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Recently, competing endogenous RNAs (ceRNA) have revealed a significant role in the progression of HCC. Herein, we aimed to construct a ceRNA network to identify potential biomarkers and illustrate its correlation with immune infiltration in HCC.MethodsRNA sequencing data and clinical traits of HCC patients were downloaded from TCGA. The limma R package was used to identify differentially expressed (DE) RNAs. The predicted prognostic model was established using univariate and multivariate Cox regression. A K-M curve, TISIDB and GEPIA website were utilized for survival analysis. Functional annotation was determined using Enrichr and Reactome. Protein-to-protein network analysis was implemented using SRTNG and Cytoscape. Hub gene expression was validated by quantitative polymerase chain reaction, Oncomine and the Hunan Protein Atlas database. Immune infiltration was analyzed by TIMMER, and Drugbank was exploited to identify bioactive compounds.ResultsThe predicted model that was established revealed significant efficacy with 3- and 5-years of the area under ROC at 0.804 and 0.744, respectively. Eleven DEmiRNAs were screened out by a K-M survival analysis. Then, we constructed a ceRNA network, including 56 DElncRNAs, 6 DEmiRNAs, and 28 DEmRNAs. The 28 DEmRNAs were enriched in cancer-related pathways, for example, the TNF signaling pathway. Moreover, six hub genes, CEP55, DEPDC1, KIF23, CLSPN, MYBL2, and RACGAP1, were all overexpressed in HCC tissues and independently correlated with survival rate. Furthermore, expression of hub genes was related to immune cell infiltration in HCC, including B cells, CD8+ T cells, CD4+ T cells, monocytes, macrophages, neutrophils, and dendritic cells.ConclusionThe findings from this study demonstrate that CEP55, DEPDC1, KIF23, CLSPN, MYBL2, and RACGAP1 are closely associated with prognosis and immune infiltration, representing potential therapeutic targets or prognostic biomarkers in HCC.

scholarly journals HMGCS2 in metabolic pathways was associated with overall survival in hepatocellular carcinoma: A LASSO-derived study

2021 ◽  
Vol 104 (3) ◽  
pp. 003685042110317
Author(s):  
Rongrong Ding ◽  
Tianyou Chen ◽  
Yuan Zhang ◽  
Xiaorong Chen ◽  
Liping Zhuang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Metabolic Pathways ◽  
Mononuclear Cells ◽  
Cox Regression ◽  
Tumor Staging ◽  
The Cancer Genome Atlas ◽  
Peripheral Blood Mononuclear ◽  
Advanced Tumor ◽  
Functional Pathways

This integrated bioinformatic study aimed to investigate potential prognostic candidates in hepatocellular carcinoma (HCC). In the GSE14520, GSE101685, and The Cancer Genome Atlas (TCGA) datasets, differentially expressed genes (DEGs) were identified and functional pathways of common DEGs were enriched. The least absolute shrinkage and selection operator (LASSO) model was used to screen the potential parameters associated with overall survival (OS) in HCC patients. Metabolic pathways were the most significantly enriched functional pathways of common DEGs in these three datasets. After LASSO model analysis, HMGCS2, UGP2, BCLC staging and TNM staging were screened as potential prognostic candidates for OS in HCC patients in GSE14520. HMGCS2 in the metabolic pathway was significantly downregulated in tumor tissues and peripheral blood mononuclear cells in HCC patients (all p < 0.05). Cox regression model indicated that HMGCS2 might be associate with OS in HCC patients in GSE14520 and in the TCGA ( p = 0.029 and p = 0.05, respectively). Kaplan–Meier analysis demonstrated that HMGCS2 downregulation in tumors contributed to an unfavorable OS in HCC patients, both in GSE14520 and in the TCGA ( p = 0.0001 and p = 0.0002, respectively). Additionally, HMGCS2 was significantly downregulated in HCC patients with high alpha-fetoprotein (AFP), main tumor size >5 cm, multinodular, advanced tumor staging including BCLC, TNM and CLIP (all p < 0.05). HMGCS2 was involved in metabolic pathways, and downregulated HMGCS2 in tumors was associated with unfavorable OS in HCC patients.

scholarly journals Identification of Prognostic Biomarkers and Correlation with Immune Infiltrates in Hepatocellular Carcinoma Based on a Competing Endogenous RNA Network

2020 ◽  
Author(s):  
Zhangya Pu ◽  
Yuanyuan Zhu ◽  
Xiaofang Wang ◽  
Yun Zhong ◽  
Fang Peng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Survival Analysis ◽  
Immune Cell ◽  
Cox Regression ◽  
Malignant Tumors ◽  
Prognostic Biomarkers ◽  
Hub Genes ◽  
Immune Infiltration ◽  
Cerna Network

Abstract Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Recently, competing endogenous RNAs (ceRNA) have revealed a significant role in the progression of HCC. Herein, we aimed to construct a ceRNA network to identify potential biomarkers and illustrate its correlation with immune infiltration in HCC. Methods: RNA sequencing data and clinical traits of HCC patients were downloaded from TCGA. The limma R package was used to identify differentially expressed (DE) RNAs. The predicted prognostic model was established using univariate and multivariate Cox regression. A K-M curve and GEPIA website were utilized for survival analysis. Functional annotation was determined using Enrichr and Reactome. Protein-to-protein network analysis was implemented using SRTNG and Cytoscape. Hub gene expression was validated by Oncomine and the Hunan Protein Atlas database. Immune infiltration was analyzed by TIMMER, and Drugbank was exploited to identify bioactive compounds. Results: The predicted model that was established revealed significant efficacy with 3- and 5-years of the area under ROC at 0.804 and 0.744, respectively. Eleven DEmiRNAs were screened out by a K-M survival analysis. Then, we constructed a ceRNA network, including 56 DElncRNAs, 6 DEmiRNAs, and 28 DEmRNAs. The 28 DEmRNAs were enriched in cancer-related pathways, for example, the TNF signaling pathway. Moreover, six hub genes, CEP55, DEPDC1, KIF23, CLSPN, MYBL2, and RACGAP1, were all overexpressed in HCC tissues and independently correlated with survival rate. Furthermore, expression of hub genes was related to immune cell infiltration in HCC, including B cells, CD8 + T cells, CD4 + T cells, monocytes, macrophages, neutrophils, and dendritic cells. Conclusions: The findings from this study demonstrate that CEP55, DEPDC1, KIF23, CLSPN, MYBL2, and RACGAP1 are closely associated with prognosis and immune infiltration, representing potential therapeutic targets or prognostic biomarkers in HCC.

scholarly journals Identification of Immune-Related Prognostic mRNA and lncRNA in Patients with Hepatocellular Carcinoma

2022 ◽  
Vol 2022 ◽  
pp. 1-16
Author(s):  
Dan Chen ◽  
Xiaoting Li ◽  
Hui Li ◽  
Kai Wang ◽  
Xianghua Tian
Keyword(s):  
Hepatocellular Carcinoma ◽  
Flow Cytometry ◽  
T Cells ◽  
Regression Analysis ◽  
Survival Analysis ◽  
Immune Cells ◽  
Cox Regression ◽  
Differentially Expressed ◽  
Cox Regression Analysis ◽  
Immune Related Genes

Background. As the most common hepatic malignancy, hepatocellular carcinoma (HCC) has a high incidence; therefore, in this paper, the immune-related genes were sought as biomarkers in liver cancer. Methods. In this study, a differential expression analysis of lncRNA and mRNA in The Cancer Genome Atlas (TCGA) dataset between the HCC group and the normal control group was performed. Enrichment analysis was used to screen immune-related differentially expressed genes. Cox regression analysis and survival analysis were used to determine prognostic genes of HCC, whose expression was detected by molecular experiments. Finally, important immune cells were identified by immune cell infiltration and detected by flow cytometry. Results. Compared with the normal group, 1613 differentially expressed mRNAs (DEmRs) and 1237 differentially expressed lncRNAs (DElncRs) were found in HCC. Among them, 143 immune-related DEmRs and 39 immune-related DElncRs were screened out. These genes were mainly related to MAPK cascade, PI3K-AKT signaling pathway, and TGF-beta. Through Cox regression analysis and survival analysis, MMP9, SPP1, HAGLR, LINC02202, and RP11-598F7.3 were finally determined as the potential diagnostic biomarkers for HCC. The gene expression was verified by RT-qPCR and western blot. In addition, CD4 + memory resting T cells and CD8 + T cells were identified as protective factors for overall survival of HCC, and they were found highly expressed in HCC through flow cytometry. Conclusion. The study explored the dysregulation mechanism and potential biomarkers of immune-related genes and further identified the influence of immune cells on the prognosis of HCC, providing a theoretical basis for the prognosis prediction and immunotherapy in HCC patients.

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

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.

scholarly journals Downregulation of Brain Enriched Type 2 MAGEs Is Associated With Immune Infiltration and Poor Prognosis in Glioma

2020 ◽  
Vol 10 ◽  
Author(s):  
Mohit Arora ◽  
Sarita Kumari ◽  
Jay Singh ◽  
Anita Chopra ◽  
Shyam S. Chauhan
Keyword(s):  
Dna Methylation ◽  
Hedgehog Signaling ◽  
Neuronal Development ◽  
Cox Regression ◽  
Lower Grade ◽  
Poor Overall Survival ◽  
Cox Regression Analysis ◽  
Immune Infiltration ◽  
Molecular Features

Melanoma associated antigen (MAGE) is an extensively studied family of tumor-associated genes that share a common MAGE homology domain (MHD). Based upon their expression pattern, MAGE genes have been broadly classified into type 1 MAGEs (T1Ms) and type 2 MAGEs (T2Ms) categories. Interestingly, several T2Ms are highly expressed in the brain and involved in the regulation of neuronal development, differentiation, and survival. Available literature suggests possible tumor suppressor functions of a few T2Ms, while information available about their expression, regulation, and clinical significance in glioma is scanty. This prompted us to perform a comprehensive analysis of T2M expression in glioma. Gene expression data from glioma datasets: Oncomine, TCGA, and REMBRANDT study, were used to assess the mRNA expression of T2M genes (MAGED1, MAGED2, MAGED3, MAGED4, MAGED4B, MAGEE1, MAGEE2, MAGEF1, MAGEH1, MAGEL2, NSMCE3, and NDN), and their association with clinical characteristics and composition of the tumor microenvironment. Further, mutation, copy number alteration, and DNA methylation data from TCGA were assessed for determining potential mechanisms of T2Ms expression in glioma. Expression analysis revealed overexpression of MAGED subfamily genes in glioma, while other genes of this family exhibited reduced expression in advanced grades of this malignancy. Further, the expression of T2Ms exhibited varying extent of positive correlations with each other. Amongst downregulated T2Ms, MAGEH1 expression exhibited negative correlations with DNA methylation. Additionally, genes associated with MAGEH1 were enriched in Myc and Hedgehog signaling. Furthermore, T2Ms downregulation was associated with immune infiltration in glioma tissues and poor overall survival of glioma patients. In multivariate Cox regression analysis, MAGEH1 emerged as an independent prognosticator in lower grade glioma. Conclusively, these results suggest that expression of T2Ms is associated with important clinical and molecular features in glioma. Mechanistic studies may further provide novel insights into their role in glioma progression.

scholarly journals Transarterial Chemoembolization for the Treatment of Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis: Prognostic Factors in a Single-Center Study of 188 Patients

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Lei Liu ◽  
Cheng Zhang ◽  
Yan Zhao ◽  
Xingshun Qi ◽  
Hui Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Factors ◽  
Portal Vein ◽  
Transarterial Chemoembolization ◽  
Cox Regression ◽  
Advanced Hepatocellular Carcinoma ◽  
Portal Vein Tumor Thrombosis ◽  
Cox Regression Analysis ◽  
Tumor Thrombosis ◽  
Pugh Class

Transarterial chemoembolization (TACE) could achieve a better survival benefit than conservative treatment for advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). In this retrospective study, all HCC patients with Child-Pugh score <7 and PVTT who were consecutively admitted to our center between January 2006 and June 2012 and underwent TACE were enrolled. The efficacy and safety of TACE were analyzed. Prognostic factors were determined by Cox regression analysis. Of the 188 patients included, 89% had hepatitis B virus infection, 100% were at Barcelona Clinic Liver Cancer stage C, and 81% (n=152) and 19% (n=36) were at Child-Pugh classes A and B, respectively. The incidence of procedure-related complications was 88%. No procedure-related death was found. The median overall survival was 6.1 months. Type of PVTT (hazard ratio [HR] = 2.806), number of tumor lesions (HR = 2.288), Child-Pugh class (HR = 2.981), and presence of metastasis (HR = 1.909) were the independent predictors of survival. In conclusion, TACE could be selectively used for the treatment of advanced HCC with PVTT. But a high rate of postoperative adverse events should not be undermined in spite of no procedure-related death. Preoperative type of PVTT, number of tumor lesions, Child-Pugh class, and metastasis could predict the prognosis of these patients.

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

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.

Sign in / Sign up

Export Citation Format

Share Document