The Oncogenic Role of CENPA in Hepatocellular Carcinoma Development: Evidence from Bioinformatic Analysis

Objective. This study is aimed at investigating the predictive value of CENPA in hepatocellular carcinoma (HCC) development. Methods. Using integrated bioinformatic analysis, we evaluated the CENPA mRNA expression in tumor and adjacent tissues and correlated it with HCC survival and clinicopathological features. A Cox regression hazard model was also performed. Results. CENPA mRNA was significantly upregulated in tumor tissues compared with that in adjacent tissues, which were validated in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) series (all P<0.01). In the Kaplan-Meier plotter platform, the high level of CENPA mRNA was significantly correlated with overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS), and progression-free survival (PFS) in HCC patients (all log rank P<0.01). For validation in GSE14520 and pan-TCGA dataset, HCC patients with CNEPA mRNA overexpression had poor OS compared with those with low CENPA mRNA (log rank P=0.025 and P<0.0001, respectively), and those with high CENPA had poor DFS in TCGA (log rank P=0.0001). Additionally, CENPA mRNA were upregulated in HCC patients with alpha-fetoprotein (AFP) elevation, advanced TNM stage, larger tumor size, advanced AJCC stage, advanced pathology grade, and vascular invasion (all P<0.05). A Cox regression model including CENPA, OIP5, and AURKB could predict OS in HCC patients effectively (AUC=0.683). Conclusion. Overexpressed in tumors, CENPA might be an oncogenic factor in the development of HCC patients.

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High Squalene Epoxidase in Tumors Predicts Worse Survival in Patients With Hepatocellular Carcinoma: Integrated Bioinformatic Analysis on NAFLD and HCC

Cancer Control ◽

10.1177/1073274820914663 ◽

2020 ◽

Vol 27 (1) ◽

pp. 107327482091466

Author(s):

Tingting Shen ◽

Yunfei Lu ◽

Qin Zhang

Keyword(s):

Hepatocellular Carcinoma ◽

Messenger Rna ◽

Disease Free Survival ◽

Bioinformatic Analysis ◽

Gene Expression Omnibus ◽

The Cancer Genome Atlas ◽

Squalene Epoxidase ◽

Nonalcoholic Fatty Liver ◽

Kaplan Meier ◽

High Level

This study aimed to identify candidate biomarkers for predicting outcomes in nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC). Using Gene Expression Omnibus and The Cancer Genome Atlas (TCGA) databases, we identified common upregulated differential expressed genes (DEGs) in patients with NAFLD/nonalcoholic steatohepatitis (NASH) and HCC and conducted survival analysis of these upregulated DEGs with HCC outcomes. Two common upregulated DEGs including squalene epoxidase (SQLE) and EPPK1 messenger RNA (mRNA) were significantly upregulated in NAFLD, NASH, and HCC tissues, both in GSE45436 ( P < .001) and TCGA profile ( P < .001). Both SQLE and EPPK1 mRNA were upregulated in 15.56% and 8.06% patients with HCC in TCGA profile. Overexpression of SQLE in tumors was significantly associated with worse overall survival (OS) and disease-free survival (DFS) in patients with HCC (log-rank P = .027 and log-rank P = .048, respectively), while no statistical significances of OS and DFS were found in EPPK1 groups (both log-rank P > .05). For validation, SQLE upregulation contributed to significantly worse OS in patients wih HCC using Kaplan-Meier plotter analysis (hazard ratio = 1.43, 95% confidence interval: 1.01-2.02, log-rank P = .043). In addition, high level of SQLE significantly associated with advanced neoplasm histologic grade, advanced AJCC stage, and α-fetoprotein elevation ( P = .036, .045, and .029, respectively). Squalene epoxidase is associated with OS and DFS and serves as a novel prognostic biomarker for patients with HCC.

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Identification of ARHGEF38, NETO2, GOLM1, and SAPCD2 Associated With Prostate Cancer Progression by Bioinformatic Analysis and Experimental Validation

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.718638 ◽

2021 ◽

Vol 9 ◽

Author(s):

Zhuolun Sun ◽

Yunhua Mao ◽

Xu Zhang ◽

Shuo Lu ◽

Hua Wang ◽

...

Keyword(s):

Gene Expression ◽

Prostate Cancer ◽

Cancer Progression ◽

Cox Regression ◽

Prognostic Indicator ◽

Bioinformatic Analysis ◽

Gene Expression Omnibus ◽

The Cancer Genome Atlas ◽

Prognostic Signature ◽

Tcga Dataset

Prostate cancer (PCa) represents one of the most prevalent types of cancers and is a large health burden for men. The pathogenic mechanisms of PCa still need further investigation. The aim of this study was to construct an effective signature to predict the prognosis of PCa patients and identify the biofunctions of signature-related genes. First, we screened differentially expressed genes (DEGs) between PCa and normal control tissues in The Cancer Genome Atlas (TCGA) and GSE46602 datasets, and we performed weighted gene co-expression network analysis (WGCNA) to determine gene modules correlated with tumors. In total, 124 differentially co-expressed genes were retained. Additionally, five genes (ARHGEF38, NETO2, PRSS21, GOLM1, and SAPCD2) were identified to develop the prognostic signature based on TCGA dataset. The five-gene risk score was verified as an independent prognostic indicator through multivariate Cox regression analyses. The expression of the five genes involved in the signature was detected in the Gene Expression Omnibus (GEO), Gene Expression Profiling Interactive Analysis (GEPIA), and Oncomine databases. In addition, we utilized DiseaseMeth 2.0 and MEXPRESS for further analysis and found that abnormal methylation patterns may be a potential mechanism for these five DEGs in PCa. Finally, we observed that these genes, except PRSS21, were highly expressed in tumor samples and PCa cells. Functional experiments revealed that silencing ARHGEF38, NETO2, GOLM1, and SAPCD2 suppressed the proliferation, migration, and invasiveness of PCa cells. In summary, this prognostic signature had significant clinical significance for treatment planning and prognostic evaluation of patients with PCa. Thus, ARHGEF38, NETO2, GOLM1, and SAPCD2 may serve as oncogenes in PCa.

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Carcinogenesis effects of E2F transcription factor 8 (E2F8) in hepatocellular carcinoma outcomes: an integrated bioinformatic report

Bioscience Reports ◽

10.1042/bsr20193212 ◽

2020 ◽

Vol 40 (2) ◽

Cited By ~ 1

Author(s):

Ying Lü ◽

Jing Zhang ◽

Lei Li ◽

Shun Li ◽

Zongguo Yang

Keyword(s):

Hepatocellular Carcinoma ◽

Transcription Factor ◽

Cox Regression ◽

Enrichment Analysis ◽

Progression Free Survival ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Peripheral Blood Mononuclear ◽

Free Survival ◽

E2f Transcription Factor

Abstract This report aimed to investigate the carcinogenesis effects of E2F transcription factor 8 (E2F8) in hepatocellular carcinoma (HCC). E2F8 expression level was compared in Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA) and Oncomine. Survival analysis of E2F8 for HCC were conducted in Kaplan–Meier plotter. Correlations of E2F8 and clinico-pathological features were performed in TCGA. Enrichment of interacted and similar genes with E2F8 was evaluated in Gene Set Enrichment Analysis (GSEA) and Metascape. We found that E2F8 was significantly up-regulated in tumor tissues compared with nontumor tissues (all P < 0.01). Moreover, E2F8 was significantly overexpressed in peripheral blood mononuclear cell (PBMC) in HCC patients than that in healthy individuals (P < 0.001). Meta-analysis in Oncomine database confirmed that E2F8 was significantly higher in HCC tumors (P = 4.28E-08). Additionally, E2F8 elevation significantly correlated with overall survival (OS), recurrence-free survival (RFS), disease-specific survival (DSS) and progression-free survival (PFS) in HCC patients (all P < 0.01). E2F8 level was significantly higher in HCC patients with advanced neoplasm histologic grade, American Joint Committee on Cancer (AJCC) stage and α-fetoprotein (AFP) elevation (all P < 0.05). Cox regression model demonstrated that high E2F8 was an independent risk factor for OS and DFS in HCC patients (HR = 2.16, P = 0.003 and HR = 1.64, P = 0.002, respectively). Enrichment analysis revealed that genes interacted/similar with E2F8 were mainly enriched in cell cycle pathways/biological process. Conclusively, up-regulated in tumors, E2F8 might accelerate tumor progression and result in unfavorable outcomes in HCC patients.

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Development of an Aerobic Glycolysis Index for Predicting the Sorafenib Sensitivity and Prognosis of Hepatocellular Carcinoma

Frontiers in Oncology ◽

10.3389/fonc.2021.637971 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yu Pan ◽

Geng-yuan Hu ◽

Shi Jiang ◽

Shun-jie Xia ◽

Hendi Maher ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Aerobic Glycolysis ◽

Disease Free Survival ◽

The Cancer Genome Atlas ◽

Free Survival ◽

Sorafenib Therapy ◽

Tumor Tissues ◽

Cancer Genome Atlas ◽

Advanced Stages ◽

Disease Free

Hepatocellular carcinoma (HCC) is a deadly tumor with high heterogeneity. Aerobic glycolysis is a common indicator of tumor growth and plays a key role in tumorigenesis. Heterogeneity in distinct metabolic pathways can be used to stratify HCC into clinically relevant subgroups, but these have not yet been well-established. In this study, we constructed a model called aerobic glycolysis index (AGI) as a marker of aerobic glycolysis using genomic data of hepatocellular carcinoma from The Cancer Genome Atlas (TCGA) project. Our results showed that this parameter inferred enhanced aerobic glycolysis activity in tumor tissues. Furthermore, high AGI is associated with poor tumor differentiation and advanced stages and could predict poor prognosis including reduced overall survival and disease-free survival. More importantly, the AGI could accurately predict tumor sensitivity to Sorafenib therapy. Therefore, the AGI may be a promising biomarker that can accurately stratify patients and improve their treatment efficacy.

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Identification and validation of AKR1C1/2/3 as hepatocellular carcinoma risk modules via an integrated strategy

10.21203/rs.2.24543/v1 ◽

2020 ◽

Author(s):

Mingxing Xu ◽

Yuesi Zhong ◽

Fangji Yang ◽

Kai Liu ◽

Baoding Zhuang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cox Regression ◽

Significant Risk ◽

Reduction Process ◽

Progression Free Survival ◽

Tumor Stage ◽

Genetic Alterations ◽

Metabolic Process ◽

Free Survival ◽

Cox Regression Analysis

Abstract Background The human aldo-keto reductase 1 (AKR1) C family comprises four enzymes, AKR1C1–AKR1C4. Lots of studies have investigated the function of AKR1Cs in tumors, however little is known in hepatocellular carcinoma (HCC). Methods Public databases were used to explore expression and role of AKR1Cs in HCC. Meanwhile, data of 134 HCC patients from Firebrowse website was used for validation. Results The results revealed that AKR1Cs expression was negatively correlated with the infiltration level of CD4+ T cells. Overexpression of AKR1C1/2/3 was significantly associated with tumor stage and pathological grade. Moreover, higher mRNA expression of AKR1C1/2/3 was related with shorter overall survival (OS), progression-free survival (PFS) and relapse-free survival (RFS). Multivariate Cox regression analysis showed that AKR1C1/2/3 could be significant risk factors for HCC patients. Additionally, genetic alterations of AKR1Cs can significantly affect patient OS and PFS, and expression of AKR1Cs was linked to functional networks involving oxidation-reduction process, cellular hormone metabolic process and organic hydroxy compound metabolic process, as well as retinol metabolism, steroid hormone biosynthesis, metabolic pathway and fatty acid degradation pathways. Conclusions In conclusion, we successfully elaborated the relationship between AKR1Cs expression and immune infiltrations, and identified AKR1C1/2/3 could be novel prognostic biomarkers for HCC patients.

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Which Parameter Influences Local Disease-Free Survival after Radiation Therapy due to Osteolytic Metastasis? A Retrospective Study with Pre- and Post-Radiation Therapy MRI including Diffusion-Weighted Images

Journal of Clinical Medicine ◽

10.3390/jcm11010106 ◽

2021 ◽

Vol 11 (1) ◽

pp. 106

Author(s):

Ji-Yeong Lee ◽

Young-Cheol Yoon ◽

Ji-Hyun Lee ◽

Hyun-Su Kim

Keyword(s):

Radiation Therapy ◽

Treatment Response ◽

Cox Regression ◽

Disease Free Survival ◽

Progression Free Survival ◽

Maximum Diameter ◽

Tumor Diameter ◽

Free Survival ◽

Diffusion Weighted Images ◽

Local Disease

Although radiation therapy (RT) plays an important role in the palliation of localized bone metastases, there is no consensus on a reliable method for evaluating treatment response. Therefore, we retrospectively evaluated the potential of magnetic resonance imaging (MRI) using apparent diffusion coefficient (ADC) maps and conventional images in whole-tumor volumetric analysis of texture features for assessing treatment response after RT. For this purpose, 28 patients who received RT for osteolytic bone metastasis and underwent both pre- and post-RT MRI were enrolled. Volumetric ADC histograms and conventional parameters were compared. Cox regression analyses were used to determine whether the change ratio in these parameters was associated with local disease progression-free survival (LDPFS). The ADCmaximum, ADCmean, ADCmedian, ADCSD, maximum diameter, and volume of the target lesions after RT significantly increased. Change ratios of ADCmean < 1.41, tumor diameter ≥ 1.17, and tumor volume ≥ 1.55 were significant predictors of poor LDPFS. Whole-tumor volumetric ADC analysis might be utilized for monitoring patient response to RT and potentially useful in predicting clinical outcomes.

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Overexpression of lncRNA SNGH3 Predicts Unfavorable Prognosis and Clinical Outcomes in Human Cancers: Evidence from a Meta-Analysis

BioMed Research International ◽

10.1155/2020/7974034 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Yaofei Jiang ◽

Lulu Le

Keyword(s):

Clinical Outcomes ◽

Histological Grade ◽

Meta Analysis ◽

Disease Free Survival ◽

The Cancer Genome Atlas ◽

Cochrane Library ◽

Cancer Type ◽

Free Survival ◽

Human Cancers ◽

Tcga Dataset

Long noncoding RNAs (lncRNAs) have been confirmed to play a crucial role in human disease, especially in tumor development and progression. Small nucleolar RNA host gene (SNHG3), a newly identified lncRNA, has been found dysregulated in various cancers. Nevertheless, the results remain controversial. Thus, we aim to analyze the comprehensive data to elaborate the association between SNHG3 expression and clinical outcomes in multiple cancers. We searched PubMed, Web of Science, Cochrane Library, Embase, and MEDLINE database to identify eligible articles. STATA software was applied to calculate the hazard ratio (HR) and odds ratio (OR) with 95% confidence interval (95% CI) for survival outcomes and clinical parameters, respectively. Besides, the data from The Cancer Genome Atlas (TCGA) dataset was extracted to verify the results in our meta-analysis. There were thirteen studies totaling 919 cancer patients involved in this meta-analysis. The results demonstrated that high SNHG3 expression was significantly associated with poor overall survival (OS) (HR=2.53, 95% CI: 1.94-3.31) in cancers, disease-free survival (DFS) (HR=3.89, 95% CI: 1.34-11.3), and recurrence-free survival (RFS) (HR=2.42, 95% CI: 1.14-5.15) in hepatocellular carcinoma. Analysis stratified by analysis method, sample size, follow-up time, and cancer type further verified the prognostic value of SNHG3. Additionally, patients with high SNHG3 expression tended to have more advanced clinical stage, higher histological grade, earlier distant metastasis, and earlier lymph node metastasis. Excavation of TCGA dataset valuated that SNHG3 was upregulated in various cancers and predicted worse OS and DFS. Overexpressed SNHG3 was strongly associated with poor survival and clinical outcomes in human cancers and therefore can serve as a promising biomarker for predicting patients’ prognosis.

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HULC and H19 Played Different Roles in Overall and Disease-Free Survival from Hepatocellular Carcinoma after Curative Hepatectomy: A Preliminary Analysis from Gene Expression Omnibus

Disease Markers ◽

10.1155/2015/191029 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 37

Author(s):

Zongguo Yang ◽

Yunfei Lu ◽

Qingnian Xu ◽

Bozong Tang ◽

Cheol-Keun Park ◽

...

Keyword(s):

Gene Expression ◽

Risk Factors ◽

Hepatocellular Carcinoma ◽

Vascular Invasion ◽

Disease Free Survival ◽

Gene Expression Omnibus ◽

Free Survival ◽

Cox Regression Analysis ◽

Tumor Tissues ◽

Disease Free

Objective. This study aimed to evaluate the relationships between long noncoding RNAs (lncRNAs) in tumor tissues and hepatocellular carcinoma (HCC) aggressiveness and survival.Methods. We correlated the lncRNAs in tumor tissues with HCC survival and clinicopathological features based on Gene Expression Omnibus expression profile GSE36376.Results. Eight lncRNAs and 240 HCC patients were included. Cox regression analysis indicated that HULC was a positive factor for HCC overall survival (HR = 0.885, 95% CI = 0.797–0.983, andP=0.023) and disease-free survival time (HR = 0.913, 95% CI = 0.835–0.998, andP=0.045). H19 and UCA1 were both demonstrated to be risk factors of HCC disease-free survival in multivariate Cox model (HR = 1.071, 95% CI = 1.01–1.137, andP=0.022and HR = 2.4, 95% CI = 1.092–5.273, andP=0.029, resp.). But Kaplan-Meier method showed no significant association between UCA1 and HCC disease-free survival (log rankP=0.616). Logistic regression demonstrated that H19 was overexpressed in HBV-infected patients (OR = 1.14, 95% CI = 1.008–1.29, andP=0.037). HULC had a significant association with vascular invasion (OR = 0.648, 95% CI = 0.523–0.803, andP<0.001). H19 and MEG3 were both considered to be risk factors for high AFP level (OR = 1.45, 95% CI = 1.277–1.646, andP<0.001and OR = 1.613, 95% CI = 1.1–2.365, andP=0.014, resp.).Conclusions. Contributing to decreased susceptibility to vascular invasion, upregulation of HULC in tumor tissues was positively associated with HCC survival. In contrast, H19 overexpression might be risk factor for HCC aggressiveness and poor outcomes.

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Indication of Liver Transplantation for Hepatocellular Carcinoma Should Be Reconsidered in Case of Microvascular Invasion and Multilocular Tumor Occurrence

Journal of Clinical Medicine ◽

10.3390/jcm10061155 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1155

Author(s):

Jan-Paul Gundlach ◽

Stephan Schmidt ◽

Alexander Bernsmeier ◽

Rainer Günther ◽

Victor Kataev ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Transplantation ◽

Overall Survival ◽

Cox Regression ◽

Disease Free Survival ◽

Microvascular Invasion ◽

Simultaneous Occurrence ◽

Free Survival ◽

Cox Regression Analysis ◽

Disease Free

Liver transplantation (LT) is routinely performed for hepatocellular carcinoma (HCC) in cirrhosis without major vascular invasion. Although the adverse influence of microvascular invasion is recognized, its occurrence does not contraindicate LT. We retrospectively analyzed in our LT cohort the significance of microvascular invasion on survival and demonstrate bridging procedures. At our hospital, 346 patients were diagnosed with HCC, 171 patients were evaluated for LT, and 153 were listed at Eurotransplant during a period of 11 years. Among these, 112 patients received LT and were included in this study. Overall survival after 1, 3 and 5 years was 86.3%, 73.9%, and 67.9%, respectively. Microvascular invasion led to significantly reduced overall (p = 0.030) and disease-free survival (p = 0.002). Five-year disease-free survival with microvascular invasion was 10.5%. Multilocular tumor occurrence with simultaneous microvascular invasion revealed the worst prognosis. In our LT cohort, predominant bridging treatment was transarterial chemoembolization (TACE) and the number of TACE significantly correlated with poorer overall survival after LT (p = 0.028), which was confirmed in multiple Cox regression analysis for overall and disease-free survival (p = 0.015 and p = 0.011). Microvascular tumor invasion is significantly associated with reduced prognosis after LT, which is aggravated by simultaneous occurrence of multiple lesions. Therefore, indication strategies for LT should be reconsidered.

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A dual immune signature of CD8+ T Cells and MMP9 improves the survival of hepatocellular carcinoma patients

Bioscience Reports ◽

10.1042/bsr20204219 ◽

2021 ◽

Author(s):

Huan Ding ◽

Huan Hu ◽

Feifei Tian ◽

Huaping Liang

Keyword(s):

Hepatocellular Carcinoma ◽

T Cells ◽

Cd8 T Cells ◽

Immune Cells ◽

Immune Cell ◽

Cox Regression ◽

Gene Expression Omnibus ◽

The Cancer Genome Atlas ◽

High Recurrence Rate ◽

Immune Signature

The 5-year survival of hepatocellular carcinoma (HCC) is difficult due to the high recurrence rate and metastasis. Tumor infiltrating immune cells (TICs) and immune-related genes (IRGs) bring hope to improve survival and treatment of HCC patients. However, there are problems in predicting immune signatures and identifying novel therapeutic targets. In the study, the CIBERSORT algorithm was used to evaluate 22 immune cell infiltration patterns in gene expression omnibus (GEO) and the cancer genome atlas (TCGA) data. Eight immune cells were found to have significant infiltration differences between the tumor and normal groups. The CD8+ T Cells immune signature was constructed by least absolute shrinkage and selection operator (LASSO) algorithm. The high infiltration level of CD8+ T Cells could significantly improve survival of patients. The weighted gene co-expression network analysis (WGCNA) algorithm identified MMP9 was closely related to the overall survival of HCC patients. K-M survival and tROC analysis confirmed that MMP9 had an excellent prognostic prediction. Cox regression showed that a dual immune signature of CD8+ T Cells and MMP9 was independent survival factor in HCC. Therefore, a dual prognostic immune signature could improve the survival of patient and may provide a new strategy for the immunotherapy of HCC.

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