scholarly journals Increased E2F2 predicts poor prognosis in patients with HCC based on TCGA data

2020 ◽  
Author(s):  
Zhili Zeng ◽  
Zebiao Cao ◽  
Ying Tang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Dna Replication ◽  
Cox Regression ◽  
Excision Repair ◽  
Tca Cycle ◽  
Signalling Pathway ◽  
Gene Set Enrichment Analysis ◽  
Rank Test ◽  
Pyrimidine Metabolism ◽  
Citrate Cycle

Abstract Background E2F transcription factor 2(E2F2) plays an important role in the development and progression of various tumors, but its association with hepatocellular carcinoma remains unknown.The aim of our study was to investigate the role and clinical significance of E2F2 in hepatocellular carcinoma (HCC). Methods HCC raw data were extracted from TCGA. Wilcoxon signed-rank test, Kruskal-Wallis test and logistic regression was applied to analyze the the relationship between the expression of E2F2 and clinicalpathologic charateristics. Cox regression and Kaplan-Meier was employed to evaluate the correlation between clinicopathologic features and survial. The biological function of E2F2 was annotated by Gene set enrichment analysis (GSEA). Results The expression of E2F2 was increased in HCC samples. The expression of elevated E2F2 in HCC samples was prominentlly correlated with tumor grade (OR =2.62 for G3-4 vs. G1-2, p=1.80E-05), tumor stage (OR =1.74 for III-IV vs. I-II, p=0.03), topography (OR =1.64 for T3-4 vs.T1-2, p=0.04), tumor status (OR =1.88 for with tumor vs. tumor free, p= 3.79E-03), plasma AFP value (OR =3.18 for AFP≥400 vs AFP<20, p= 2.16E-04; OR=2.50 for 20≤AFP<400 vs AFP<20, p=2.56E-03). Increased E2F2 had a unfavorable OS (p=7.468e−05), PFI (p=3.183e−05), DFI (p=0.001), DSS (p=4.172e−05). Elevated E2F2 was independently bound up with OS (p = 4.4E-04, HR = 2.4 (95% CI [1.5-3.8])) and DSS (p = 7.6E-04, HR = 3.0, (95% CI [1.6-5.6])). GSEA disclosed that cell circle, RNA degradation, pyrimidine metabolism, base excision repair, aminoacyl tRNA biosynthesis, DNA replication, p53 signalling pathway, nucleotide excision repair, ubiquitin mediated proteolysis, citrate cycle TCA cycle were notably enriched in E2F2 high expression phenotype. Conclusions Elevated E2F2 can be a promissing independent prognostic biomarker and therapeutic target for HCC. Additionally, cell cycle, pyrimidine metabolism, DNA replication, p53 signalling pathway, ubiquitin mediated proteolysis, the citrate cycle TCA cycle may be the key pathway by which E2F2 participate in the initial and progression of HCC.

scholarly journals Increased E2F2 predicts poor prognosis in patients with HCC based on TCGA data

2020 ◽  
Author(s):  
Zhili Zeng ◽  
Zebiao Cao ◽  
Ying Tang
Keyword(s):  
Dna Replication ◽  
Signaling Pathway ◽  
Excision Repair ◽  
Tca Cycle ◽  
Hazard Ratio ◽  
Gene Set Enrichment Analysis ◽  
Pyrimidine Metabolism ◽  
Citrate Cycle ◽  
P53 Signaling ◽  
P53 Signaling Pathway

Abstract Background: The E2F family of transcription factor 2 (E2F2) plays an important role in the development and progression of various tumors, but its association with hepatocellular carcinoma (HCC) remains unknown. Our study aimed to investigate the role and clinical significance of E2F2 in HCC.Methods: HCC raw data were extracted from The Cancer Genome Atlas (TCGA). Wilcoxon signed-rank test, Kruskal-Wallis test and logistic regression were applied to analyze the relationship between the expression of E2F2 and clinicopathologic characteristics. Cox regression and Kaplan-Meier were employed to evaluate the correlation between clinicopathologic features and survival. The biological function of E2F2 was annotated by Gene Set Enrichment Analysis (GSEA).Results: The expression of E2F2 was increased in HCC samples. The expression of elevated E2F2 in HCC samples was prominently correlated with histologic grade (OR =2.62 for G3-4 vs. G1-2, p=1.80E-05), clinical stage (OR =1.74 for III-IV vs. I-II, p=0.03), T (OR =1.64 for T3-4 vs.T1-2, p=0.04), tumor status (OR =1.88 for with tumor vs. tumor free, p= 3.79E-03), plasma alpha fetoprotein (AFP) value (OR =3.18 for AFP≥400 vs AFP＜20, p= 2.16E-04; OR=2.50 for 20≤AFP＜400 vs AFP＜20, p=2.56E-03). Increased E2F2 had an unfavorable OS (p=7.468e−05), PFI (p=3.183e−05), DFI (p=0.001), DSS (p=4.172e−05). Elevated E2F2 was independently bound up with OS (p =0.004, hazard ratio [HR]= 2.4 (95% CI [1.3-4.2])), DFI (P =0.029, hazard ratio [HR] = 2.0 (95% CI [1.1-3.7])) and PFI (P =0.005, hazard ratio [HR] = 2.2 (95% CI [1.3-3.9])). GSEA disclosed that cell circle, RNA degradation, pyrimidine metabolism, base excision repair, aminoacyl tRNA biosynthesis, DNA replication, p53 signaling pathway, nucleotide excision repair, ubiquitin-mediated proteolysis, citrate cycle TCA cycle were notably enriched in E2F2 high expression phenotype.Conclusions: Elevated E2F2 can be a promising independent prognostic biomarker and therapeutic target for HCC. Additionally, cell cycle, pyrimidine metabolism, DNA replication, p53 signaling pathway, ubiquitin-mediated proteolysis, the citrate cycle TCA cycle may be the key pathway by which E2F2 participates in the initial and progression of HCC.

scholarly journals Increased E2F2 predicts poor prognosis in patients with HCC based on TCGA data

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Zhili Zeng ◽  
Zebiao Cao ◽  
Ying Tang
Keyword(s):  
Dna Replication ◽  
Signaling Pathway ◽  
Excision Repair ◽  
Tca Cycle ◽  
Hazard Ratio ◽  
Gene Set Enrichment Analysis ◽  
Pyrimidine Metabolism ◽  
Citrate Cycle ◽  
P53 Signaling ◽  
P53 Signaling Pathway

Abstract Background The E2F family of transcription factor 2 (E2F2) plays an important role in the development and progression of various tumors, but its association with hepatocellular carcinoma (HCC) remains unknown. Our study aimed to investigate the role and clinical significance of E2F2 in HCC. Methods HCC raw data were extracted from The Cancer Genome Atlas (TCGA). Wilcoxon signed-rank test, Kruskal-Wallis test and logistic regression were applied to analyze the relationship between the expression of E2F2 and clinicopathologic characteristics. Cox regression and Kaplan-Meier were employed to evaluate the correlation between clinicopathologic features and survival. The biological function of E2F2 was annotated by Gene Set Enrichment Analysis (GSEA). Results The expression of E2F2 was increased in HCC samples. The expression of elevated E2F2 in HCC samples was prominently correlated with histologic grade (OR = 2.62 for G3–4 vs. G1–2, p = 1.80E-05), clinical stage (OR = 1.74 for III-IV vs. I-II, p = 0.03), T (OR = 1.64 for T3–4 vs.T1–2, p = 0.04), tumor status (OR = 1.88 for with tumor vs. tumor free, p = 3.79E-03), plasma alpha fetoprotein (AFP) value (OR = 3.18 for AFP ≥ 400 vs AFP<20, p = 2.16E-04; OR = 2.50 for 20 ≤ AFP<400 vs AFP<20, p = 2.56E-03). Increased E2F2 had an unfavorable OS (p = 7.468e− 05), PFI (p = 3.183e− 05), DFI (p = 0.001), DSS (p = 4.172e− 05). Elevated E2F2 was independently bound up with OS (p = 0.004, hazard ratio [HR] = 2.4 (95% CI [1.3–4.2])), DFI (P = 0.029, hazard ratio [HR] = 2.0 (95% CI [1.1–3.7])) and PFI (P = 0.005, hazard ratio [HR] = 2.2 (95% CI [1.3–3.9])). GSEA disclosed that cell circle, RNA degradation, pyrimidine metabolism, base excision repair, aminoacyl tRNA biosynthesis, DNA replication, p53 signaling pathway, nucleotide excision repair, ubiquitin-mediated proteolysis, citrate cycle TCA cycle were notably enriched in E2F2 high expression phenotype. Conclusions Elevated E2F2 can be a promising independent prognostic biomarker and therapeutic target for HCC. Additionally, cell cycle, pyrimidine metabolism, DNA replication, p53 signaling pathway, ubiquitin-mediated proteolysis, the citrate cycle TCA cycle may be the key pathway by which E2F2 participates in the initial and progression of HCC.

scholarly journals Increased E2F2 predicts poor prognosis in patients with HCC based on TCGA data

2020 ◽  
Author(s):  
Zhili Zeng ◽  
Zebiao Cao ◽  
Ying Tang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Dna Replication ◽  
Signaling Pathway ◽  
Excision Repair ◽  
Tca Cycle ◽  
Hazard Ratio ◽  
Pyrimidine Metabolism ◽  
Citrate Cycle ◽  
P53 Signaling ◽  
P53 Signaling Pathway

Abstract Background: The E2F family of transcription factor 2 (E2F2) plays an important role in the development and progression of various tumors, but its association with hepatocellular carcinoma remains unknown. The aim of our study was to investigate the role and clinical significance of E2F2 in hepatocellular carcinoma (HCC).Methods: HCC raw data were extracted from The Cancer Genome Atlas (TCGA). Wilcoxon signed-rank test, Kruskal-Wallis test and logistic regression was applied to analyze the relationship between the expression of E2F2 and clinicopathologic characteristics. Cox regression and Kaplan-Meier was employed to evaluate the correlation between clinicopathologic features and survival. The biological function of E2F2 was annotated by Gene set enrichment analysis (GSEA).Results: The expression of E2F2 was increased in HCC samples. The expression of elevated E2F2 in HCC samples was prominently correlated with histologic grade (OR =2.62 for G3-4 vs. G1-2, p=1.80E-05), clinical stage (OR =1.74 for III-IV vs. I-II, p=0.03), T (OR =1.64 for T3-4 vs.T1-2, p=0.04), tumor status (OR =1.88 for with tumor vs. tumor free, p= 3.79E-03), plasma alpha fetoprotein (AFP) value (OR =3.18 for AFP≥400 vs AFP＜20, p= 2.16E-04; OR=2.50 for 20≤AFP＜400 vs AFP＜20, p=2.56E-03). Increased E2F2 had an unfavorable OS (p=7.468e−05), PFI (p=3.183e−05), DFI (p=0.001), DSS (p=4.172e−05). Elevated E2F2 was independently bound up with OS (p =0.004 , hazard ratio [HR]= 2.4 (95% CI [1.3-4.2])), DFI (P =0.029, hazard ratio [HR] = 2.0 (95% CI [1.1-3.7])) and PFI (P =0.005, hazard ratio [HR] = 2.2 (95% CI [1.3-3.9])) . GSEA disclosed that cell circle, RNA degradation, pyrimidine metabolism, base excision repair, aminoacyl tRNA biosynthesis, DNA replication, p53 signaling pathway, nucleotide excision repair, ubiquitin mediated proteolysis, citrate cycle TCA cycle were notably enriched in E2F2 high expression phenotype.Conclusions: Elevated E2F2 can be a promising independent prognostic biomarker and therapeutic target for HCC. Additionally, cell cycle, pyrimidine metabolism, DNA replication, p53 signaling pathway, ubiquitin mediated proteolysis, the citrate cycle TCA cycle may be the key pathway by which E2F2 participate in the initial and progression of HCC.

scholarly journals Increased E2F2 predicts poor prognosis in patients with HCC based on TCGA data

2020 ◽  
Author(s):  
Zhili Zeng ◽  
Zebiao Cao ◽  
Ying Tang
Keyword(s):  
Dna Replication ◽  
Signaling Pathway ◽  
Excision Repair ◽  
Tca Cycle ◽  
Hazard Ratio ◽  
Gene Set Enrichment Analysis ◽  
Pyrimidine Metabolism ◽  
Citrate Cycle ◽  
P53 Signaling ◽  
P53 Signaling Pathway

Abstract Background: The E2F family of transcription factor 2 (E2F2) plays an important role in the development and progression of various tumors, but its association with hepatocellular carcinoma (HCC) remains unknown. Our study aimed to investigate the role and clinical significance of E2F2 in HCC.Methods: HCC raw data were extracted from The Cancer Genome Atlas (TCGA). Wilcoxon signed-rank test, Kruskal-Wallis test and logistic regression were applied to analyze the relationship between the expression of E2F2 and clinicopathologic characteristics. Cox regression and Kaplan-Meier were employed to evaluate the correlation between clinicopathologic features and survival. The biological function of E2F2 was annotated by Gene Set Enrichment Analysis (GSEA).Results: The expression of E2F2 was increased in HCC samples. The expression of elevated E2F2 in HCC samples was prominently correlated with histologic grade (OR =2.62 for G3-4 vs. G1-2, p=1.80E-05), clinical stage (OR =1.74 for III-IV vs. I-II, p=0.03), T (OR =1.64 for T3-4 vs.T1-2, p=0.04), tumor status (OR =1.88 for with tumor vs. tumor free, p= 3.79E-03), plasma alpha fetoprotein (AFP) value (OR =3.18 for AFP≥400 vs AFP＜20, p= 2.16E-04; OR=2.50 for 20≤AFP＜400 vs AFP＜20, p=2.56E-03). Increased E2F2 had an unfavorable OS (p=7.468e−05), PFI (p=3.183e−05), DFI (p=0.001), DSS (p=4.172e−05). Elevated E2F2 was independently bound up with OS (p =0.004, hazard ratio [HR]= 2.4 (95% CI [1.3-4.2])), DFI (P =0.029, hazard ratio [HR] = 2.0 (95% CI [1.1-3.7])) and PFI (P =0.005, hazard ratio [HR] = 2.2 (95% CI [1.3-3.9])). GSEA disclosed that cell circle, RNA degradation, pyrimidine metabolism, base excision repair, aminoacyl tRNA biosynthesis, DNA replication, p53 signaling pathway, nucleotide excision repair, ubiquitin-mediated proteolysis, citrate cycle TCA cycle were notably enriched in E2F2 high expression phenotype.Conclusions: Elevated E2F2 can be a promising independent prognostic biomarker and therapeutic target for HCC. Additionally, cell cycle, pyrimidine metabolism, DNA replication, p53 signaling pathway, ubiquitin-mediated proteolysis, the citrate cycle TCA cycle may be the key pathway by which E2F2 participates in the initial and progression of HCC.

scholarly journals Analysis of HSD11B2 as a prognostic marker in Melanoma via TCGA data mining

2020 ◽  
Author(s):  
Hongyi Fu ◽  
Yaqin Tang ◽  
Ying Ding
Keyword(s):  
Cox Regression ◽  
Signalling Pathway ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Rank Test ◽  
Clinicopathologic Characteristics ◽  
Data Set ◽  
Receptor Signalling ◽  
Pathologic Features ◽  
Melanoma Patients

Abstract Background: Hydroxysteroid 11-Beta Dehydrogenase 2 (HSD11B2) expression has been reported to be present in melanoma. We investigated the association of HSD11B2 with melanoma using publicly available data from The Cancer Genome Atlas (TCGA). Methods: The relationship between clinical pathologic features and HSD11B2 were analysed via Wilcoxon signed-rank test and logistic regression. Clinicopathologic characteristics associated with overall survival in melanoma patients were calculated using Cox regression and the Kaplan-Meier method. Gene Set Enrichment Analysis (GSEA) and gene co-association of HSD11B2 were performed using TCGA data set. Results: Reduced HSD11B2 expression was significantly lower in melanoma patients compared to normal patients (p value = 3.004e-122) and also associated with lower survivability. low HSD11B2 expression in melanoma was also significantly associated with cancer stages T (p value = 0.002) and N (p value < 0.001) and age (p value = 0.003). Genes TFCP2L1, PRR15L, ATP6V1B1, C9orf152, AC009948.1, AL391244.1, WDCP, HNRNPCP2 and GTF2E1 were all shown to be co-associated with changes in HSD1B2 expression. Multiple signalling pathway including cytosolic DNA sensing pathway, JAK STAT signalling pathway, NOD like receptor signalling pathway, T cell receptor signalling pathway and Toll like receptor signalling pathway were differentially enriched in low HSD11B2 expression phenotype. Conclusion: Our study revealed that HSD11B2 expression is closely associated with melanoma development and age, as well as multiple cancer related genes and pathways, thus highlighting HSD11B2 as a potential therapeutic marker of melanoma.

scholarly journals LncRNA ELF3-AS1 is a Prognostic Biomarker and Correlated with Immune Infiltrates in Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Tianming Chen ◽  
Changhao Zhu ◽  
Xing Wang ◽  
Yaozhen Pan
Keyword(s):  
Hepatocellular Carcinoma ◽  
Noncoding Rna ◽  
Cox Regression ◽  
Radioligand Binding ◽  
Gene Set Enrichment Analysis ◽  
Rank Test ◽  
Hepatic Tissue ◽  
Poor Overall Survival ◽  
Cox Regression Analysis ◽  
The Relationship

Background. Expression of long noncoding RNA (lncRNA) ELF3 antisense RNA 1 (ELF3-AS1) is observed in some cancers, while its role in hepatocellular carcinoma (HCC) is unclear. The study aimed to investigate the relationship between ELF3-AS1 and HCC based on database, bioinformatics, and statistical analysis. Methods. In this study, Kruskal–Wallis test, Wilcoxon sign-rank test, logistic regression, Kaplan–Meier method, Cox regression analysis, gene set enrichment analysis (GSEA), and immunoinfiltration analysis were used to assess the relationship between ELF3-AS1 expression and clinical characteristics of HCC patients, the relationship between ELF3-AS1 expression and prognosis of HCC patients, and the possible functions of ELF3-AS1 in HCC. Results. High expression of ELF3-AS1 in patients with HCC was related to T stage ( P  < 0.001), gender ( P  = 0.006), residual tumor ( P  = 0.008), histologic grade ( P  < 0.001), adjacent hepatic tissue inflammation ( P  = 0.011), AFP ( P  < 0.001), and vascular invasion ( P  = 0.028). High ELF3-AS1 expression was associated with poor overall survival (OS) ( P  = 0.001) and DSS ( P  = 0.047). ELF3-AS1 expression ( P  = 0.011) was independently correlated with OS in HCC patients. In the high ELF3-AS1 expression group, GPCR-radioligand binding, M phase, Class A/1 (rhodopsin-like receptors), cell cycle checkpoints, translation, mitotic metaphase and anaphase, signaling by robo receptors, keratinization, and rRNA processing were differentially enriched by GESA. ELF3-AS1 expression was associated with immune infiltrating cells. Conclusions. ELF3-AS1 expression was associated with poor prognosis in HCC. ELF3-AS1 expression was significantly associated with immune infiltration. ELF3-AS1 is a promising biomarker that can be used for the diagnosis and prognosis of HCC.

scholarly journals Identification of a five-gene signature in association with overall survival for hepatocellular carcinoma

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11273
Author(s):  
Lei Yang ◽  
Weilong Yin ◽  
Xuechen Liu ◽  
Fangcun Li ◽  
Li Ma ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Overall Survival ◽  
Cox Regression ◽  
Enrichment Analysis ◽  
Gene Signature ◽  
Gene Set Enrichment Analysis ◽  
Enrichment Score ◽  
Hub Genes ◽  
Cox Regression Analysis

Background Hepatocellular carcinoma (HCC) is considered to be a malignant tumor with a high incidence and a high mortality. Accurate prognostic models are urgently needed. The present study was aimed at screening the critical genes for prognosis of HCC. Methods The GSE25097, GSE14520, GSE36376 and GSE76427 datasets were obtained from Gene Expression Omnibus (GEO). We used GEO2R to screen differentially expressed genes (DEGs). A protein-protein interaction network of the DEGs was constructed by Cytoscape in order to find hub genes by module analysis. The Metascape was performed to discover biological functions and pathway enrichment of DEGs. MCODE components were calculated to construct a module complex of DEGs. Then, gene set enrichment analysis (GSEA) was used for gene enrichment analysis. ONCOMINE was employed to assess the mRNA expression levels of key genes in HCC, and the survival analysis was conducted using the array from The Cancer Genome Atlas (TCGA) of HCC. Then, the LASSO Cox regression model was performed to establish and identify the prognostic gene signature. We validated the prognostic value of the gene signature in the TCGA cohort. Results We screened out 10 hub genes which were all up-regulated in HCC tissue. They mainly enrich in mitotic cell cycle process. The GSEA results showed that these data sets had good enrichment score and significance in the cell cycle pathway. Each candidate gene may be an indicator of prognostic factors in the development of HCC. However, hub genes expression was weekly associated with overall survival in HCC patients. LASSO Cox regression analysis validated a five-gene signature (including CDC20, CCNB2, NCAPG, ASPM and NUSAP1). These results suggest that five-gene signature model may provide clues for clinical prognostic biomarker of HCC.

scholarly journals Clinical Value of lncRNA LUCAT1 Expression in Liver Cancer and its Potential Pathways

2019 ◽  
Vol 28 (4) ◽  
pp. 439-447 ◽  
Author(s):  
Yan Jiao ◽  
Yanqing Li ◽  
Bai Ji ◽  
Hongqiao Cai ◽  
Yahui Liu
Keyword(s):  
Liver Cancer ◽  
Roc Curve ◽  
Cox Regression ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Cancer Prognosis ◽  
Rank Test ◽  
P Value ◽  
Rna Seq ◽  
Cox Regression Analysis

Background and Aims: Emerging studies indicate that long noncoding RNAs (lncRNAs) play a role as prognostic markers in many cancers, including liver cancer. Here, we focused on the lncRNA lung cancer-associated transcript 1 (LUCAT1) for liver cancer prognosis. Methods: RNA-seq and phenotype data were downloaded from the Cancer Genome Atlas (TCGA). Chisquare tests were used to evaluate the correlations between LUCAT1 expression and clinical features. Survival analysis and Cox regression analysis were used to compare different LUCAT1 expression groups (optimal cutoff value determined by ROC). The log-rank test was used to calculate the p-value of the Kaplan-Meier curves. A ROC curve was used to evaluate the diagnostic value. Gene Set Enrichment Analysis (GSEA) was performed, and competing endogenous RNA (ceRNA) networks were constructed to explore the potential mechanism. Results: Data mining of the TCGA -Liver Hepatocellular Carcinoma (LIHC) RNA-seq data of 371 patients showed the overexpression of LUCAT1 in cancerous tissue. High LUCAT1 expression was associated with age (p=0.007), histologic grade (p=0.009), T classification (p=0.022), and survival status (p=0.002). High LUCAT1 patients had a poorer overall survival and relapse-free survival than low LUCAT1 patients. Multivariate analysis identified LUCAT1 as an independent risk factor for poor survival. The ROC curve indicated modest diagnostic performance. GSEA revealed the related signaling pathways, and the ceRNA network uncovered the underlying mechanism. Conclusion: High LUCAT1 expression is an independent prognostic factor for liver cancer.

scholarly journals Hypoxic Characteristic in the Immunosuppressive Microenvironment of Hepatocellular Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhuomao Mo ◽  
Daiyuan Liu ◽  
Dade Rong ◽  
Shijun Zhang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Cell ◽  
Cox Regression ◽  
Cancer Genome ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
Immune Checkpoints ◽  
Immune Cell Infiltration ◽  
Immunosuppressive Microenvironment

Background: Generally, hepatocellular carcinoma (HCC) exists in an immunosuppressive microenvironment that promotes tumor evasion. Hypoxia can impact intercellular crosstalk in the tumor microenvironment. This study aimed to explore and elucidate the underlying relationship between hypoxia and immunotherapy in patients with HCC.Methods: HCC genomic and clinicopathological datasets were obtained from The Cancer Genome Atlas (TCGA-LIHC), Gene Expression Omnibus databases (GSE14520) and International Cancer Genome Consortium (ICGC-LIRI). The TCGA-LIHC cases were divided into clusters based on single sample gene set enrichment analysis and hierarchical clustering. After identifying patients with immunosuppressive microenvironment with different hypoxic conditions, correlations between immunological characteristics and hypoxia clusters were investigated. Subsequently, a hypoxia-associated score was established by differential expression, univariable Cox regression, and lasso regression analyses. The score was verified by survival and receiver operating characteristic curve analyses. The GSE14520 cohort was used to validate the findings of immune cell infiltration and immune checkpoints expression, while the ICGC-LIRI cohort was employed to verify the hypoxia-associated score.Results: We identified hypoxic patients with immunosuppressive HCC. This cluster exhibited higher immune cell infiltration and immune checkpoint expression in the TCGA cohort, while similar significant differences were observed in the GEO cohort. The hypoxia-associated score was composed of five genes (ephrin A3, dihydropyrimidinase like 4, solute carrier family 2 member 5, stanniocalcin 2, and lysyl oxidase). In both two cohorts, survival analysis revealed significant differences between the high-risk and low-risk groups. In addition, compared to other clinical parameters, the established score had the highest predictive performance at both 3 and 5 years in two cohorts.Conclusion: This study provides further evidence of the link between hypoxic signals in patients and immunosuppression in HCC. Defining hypoxia-associated HCC subtypes may help reveal potential regulatory mechanisms between hypoxia and the immunosuppressive microenvironment, and our hypoxia-associated score could exhibit potential implications for future predictive models.

Risk Factors for Hepatocellular Carcinoma After Splenectomy in Liver Cirrhotic Patients

2021 ◽  
pp. 000313482110415
Author(s):  
Naruhiko Honmyo ◽  
Tsuyoshi Kobayashi ◽  
Shintaro Kuroda ◽  
Kentaro Ide ◽  
Masahiro Ohira ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Portal Hypertension ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Hemoglobin Level ◽  
Rank Test ◽  
Predictive Index ◽  
Preoperative Hemoglobin ◽  
Preoperative Hemoglobin Level

Background Splenectomy is sometimes indicated for portal hypertension caused by cirrhosis, which is a risk for hepatic carcinogenesis. This study aimed to identify risk factors for hepatocellular carcinoma (HCC) development after splenectomy. Methods This retrospective study included 65 patients who underwent splenectomy for portal hypertension between 2009 and 2017. Cox regression analyses were performed to identify factors related to HCC development after splenectomy. The predictive index for HCC development was constructed from the results of multivariate analysis, and 3 risk-dependent groups were defined. Discrimination among the groups was estimated using Kaplan-Meier curves and the log-rank test. Results Post-splenectomy, 36.9% of patients developed HCC. In the univariate analysis, the etiology of cirrhosis (hepatitis C virus antibody, P = .005, and hepatitis B surface antigen, P = .008, referring to non-B and non-C patients, respectively), presence of HCC history ( P < .001), and preoperative hemoglobin level ( P = .007) were related to HCC development, and the presence of HCC history ( P = .002) and preoperative hemoglobin level ( P = .022) were independent risk factors. The predictive index classified three groups at risk; the hazards in each group were significantly different (low vs middle risk, P = .035, and middle vs high risk, P = .011). Discussion The etiology of cirrhosis, presence of HCC history, and hemoglobin level were associated with HCC development after splenectomy. The predictive model may aid in HCC surveillance after splenectomy for patients with portal hypertension.

Sign in / Sign up

Export Citation Format

Share Document