Expression and prognostic roles of PRDXs gene family in hepatocellular carcinoma

Abstract Background As the fourth leading cause of cancer-related death in the world, the therapeutic effect and 5-year overall survival of hepatocellular carcinoma (HCC) are not optimistic. Previous researches indicated that the disorder of PRDXs was related to the occurrence and development of cancers. Methods In this study, PRDXs were found in various tumor cell lines by CCLE database analysis. The analysis results of UALCAN, HCCDB and Human Protein Atlas databases showed the expression of PRDXs mRNA and protein in HCC tissues was dysregulated. Besides, UALCAN was used to assess the correlations between PRDXs mRNA as well as methylation levels and clinical characterization. Results High expression of PRDX1 or low expression of PRDX2/3 suggested poor prognosis for HCC patients which was demonstrated by Kaplan–Meier Plotter. The genetic alterations and biological interaction network of PRDXs in HCC samples were obtained from c-Bioportal. In addition, LinkedOmics was employed to analyze PRDXs related differentially expressed genes, and on this basis, enrichment of KEGG pathway and miRNAs targets of PRDXs were conducted. The results indicated that these genes were involved in several canonical pathways and certain amino acid metabolism, some of which may effect on the progression of HCC. Conclusions In conclusion, the disordered expression of some PRDX family members was associated with the prognosis of HCC patients, suggesting that these PRDX family members may become new molecular targets for the treatment and prognosis prediction of HCC.

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Expression and Prognostic Roles of PRDXs Gene Family in Hepatocellular Carcinoma

10.21203/rs.3.rs-37315/v1 ◽

2020 ◽

Author(s):

Mingxing Xu ◽

Jianliang Xu ◽

Dun Zhu ◽

Rishun Su ◽

Baoding Zhuang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Acid Metabolism ◽

Interaction Network ◽

Public Database ◽

Kaplan Meier ◽

Online Tools ◽

Canonical Pathways ◽

Human Protein Atlas ◽

Kaplan Meier Plotter ◽

Analyze Data

Abstract Background: As the second leading cause of cancer-related death in the world, the therapeutic effect and 5-year overall survival of hepatocellular carcinoma (HCC) are not optimistic. Previous researches indicated that the disorder of PRDXs was related to the occurrence and development of cancer. Methods: In this study,analyzing through CCLE, UALCAN, HCCDB and Human Protein Atlas database databases, PRDXs not only existedin various tumor cell lines, but alsohad maladjusted expression on mRNA and protein levelsin HCC tissues. Besides, the correlations between mRNA as well as methylation levels of PRDXs and clinical characterization wereevaluated using UALCAN. Results: Kaplan-Meier Plotter demonstrated that high expression of PRDX1 or low expression of PRDX2/3 suggested poor prognosis for HCC patients. The mutation frequency, type and biological interaction network of PRDXs were obtained from c-Bioportal. By LinkedOmics,PRDXs related differential expressions geneswere obtained, which were involved in several canonical pathways and certain amino acid metabolism, as well as miRNAs targeting PRDXs, some of which may effect on the progression of HCC. Conclusions: In conclusion, using online tools to analyze data based on several public database, it was found that disordered expression of PRDXs was correlated with the prognosis of HCC patients, suggesting that PRDXs may be new molecular targets for HCC therapy and prognosis prediction.

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Expression and prognostic roles PRDXs gene family in hepatocellular carcinoma

10.21203/rs.3.rs-18264/v1 ◽

2020 ◽

Author(s):

Mingxing Xu ◽

Jianliang Xu ◽

Dun Zhu ◽

Rishun Su ◽

Baoding Zhuang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Acid Metabolism ◽

Interaction Network ◽

Tumor Cell Lines ◽

Protein Levels ◽

Kaplan Meier ◽

Online Tools ◽

Canonical Pathways ◽

Human Protein Atlas ◽

Kaplan Meier Plotter

Abstract Background: As the second leading cause of cancer-related death in the world, the therapeutic effect and 5-year overall survival of hepatocellular carcinoma (HCC) are not optimistic. Previous researches indicated that the disorder of PRDXs was related to the occurrence and development of cancer.Methods: In this study, analyzing through CCLE, UALCAN, HCCDB and Human Protein Atlas database databases, PRDXs not only existed in various tumor cell lines, but also had maladjusted expression on mRNA and protein levels in HCC tissues. Besides, the correlations between mRNA as well as methylation levels of PRDXs and clinical characterization were evaluated using UALCAN.Results: Kaplan-Meier Plotter demonstrated that high expression of PRDX1 or low expression of PRDX2/3 suggested poor prognosis for HCC patients. The mutation frequency, type and biological interaction network of PRDXs were obtained from c-Bioportal. By LinkedOmics, PRDXs related differential expressions genes were obtained, which were involved in several canonical pathways and certain amino acid metabolism, as well as miRNAs targeting PRDXs, some of which may effect on the progression of HCC.Conclusions: In conclusion, the disordered expression of PRDXs was correlated with prognosis of HCC patients analyzing by online tools, suggesting that PRDXs could be new molecular targets for HCC treatment and prognosis prediction.

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Identification of hub genes and potential drugs in hepatocellular carcinoma through integrated bioinformatics analysis

10.21203/rs.3.rs-88832/v1 ◽

2020 ◽

Author(s):

Xiaolong Chen ◽

Zhixiong Xia ◽

Yafeng Wan ◽

Ping Huang

Keyword(s):

Hepatocellular Carcinoma ◽

Disease Free Survival ◽

Interaction Network ◽

Enrichment Analysis ◽

Hub Genes ◽

Free Survival ◽

Protein Protein Interaction ◽

Kaplan Meier ◽

Human Protein Atlas ◽

Kaplan Meier Plotter

Abstract BackgroundHepatocellular carcinoma (HCC) is the third cancer-related cause of death in the world. Until now, the involved mechanisms during the development of HCC are largely unknown. This study aims to explore the driven-genes and potential drugs in HCC. MethodsThree mRNA expression datasets were used to analyze the differentially expressed genes (DEGs) in HCC. The bioinformatics approaches include identification of DEGs and hub genes, GO terms analysis and KEGG enrichment analysis, construction of protein–protein interaction network. The expression levels of hub genes were validated based on TCGA, GEPIA and the Human Protein Atlas. Moreover, overall survival and disease-free survival analysis of the hub genes were further conducted by Kaplan-Meier plotter and the GEPIA. DGIdb database was performed to search the candidate drugs for HCC. ResultsFinally, 197 DEGs were identified. The PPI network was constructed using STRING software. Then ten genes were selected and considered as the hub genes. The ten genes were all closely related to the survival of HCC patients. DGIdb database predicted 39 small molecules as the possible drugs for treating HCC. ConclusionsOur study provides some new insights into HCC pathogenesis and treatments. The candidate drugs may improve the efficiency of HCC therapy in future.

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Identification of G6PC As A Potential Prognostic Biomarker In Hepatocellular Carcinoma Based On Bioinformatics Analysis

10.21203/rs.3.rs-1031842/v1 ◽

2021 ◽

Author(s):

Tian Li ◽

Liao Yong

Keyword(s):

Hepatocellular Carcinoma ◽

T Cells ◽

Interaction Network ◽

Incidence Rates ◽

Database Analysis ◽

Poor Overall Survival ◽

Kaplan Meier ◽

Key Genes ◽

Kaplan Meier Plotter ◽

Low Expression

Abstract Background: Hepatocellular carcinoma (HCC) has high mortality and incidence rates around the world with limited therapeutic options, there is an urgent need for identification of novel therapeutic targets and biomarkers for early diagnosis and predicting patient survival with HCC. Methods: Several studies (GSE102083, GSE29722, GSE101685 and GSE112790) from the GEO database in HCC were screened and analyzed by GEO2R, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted with the Database for Annotation, Visualization and Integrated Discovery (DAVID). The protein-protein interaction network (PPI) was plotted and the module analysis was performed using Search Tool for the Retrieval of Inter-acting Genes/Proteins database (STRING) and Cytoscape. The expression and survival of key genes were identified using UALCAN, Kaplan-Meier Plotter and ONCOMINE online databases, and the immune infiltration level of key genes was analyzed via TIMER database. Results: Eight key genes were finally screened out through several database analysis, and UALCAN was used to detect the expressions of CKS2 and G6PC, which were closely related to the survival of HCC patients. Further analysis on the differential expression of G6PC in multiple cancerous tumors and normal tissues revealed low expression in many solid tumors by Oncomine and TIMER. In addition, Kaplan-Meier plotter and UALCAN database analysis to access diseases prognosis suggested that low expression of G6PC was significantly associated with poor overall survival in HCC patients. Finally, TIMER database analysis showed a significant negative correlation between G6PC and infiltration levels of six kinds of immune cells. The somatic copy number alterations (SCNAs) of G6PC were associated with B cells, CD8+ T cells, CD4+ T cells, macrophages, dentritic cells and neutrophils. Conclusions: These bioinformatic data identified G6PC as a potential key gene in the diagnosis and prognosis of HCC.

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Functional lncRNA-miRNA-mRNA Networks in Response to Baicalein Treatment in Hepatocellular Carcinoma

BioMed Research International ◽

10.1155/2021/8844261 ◽

2021 ◽

Vol 2021 ◽

pp. 1-18

Author(s):

Xin Zhao ◽

Dongyang Tang ◽

Xiaofei Chen ◽

Shaoqing Chen ◽

Cheng Wang

Keyword(s):

Hepatocellular Carcinoma ◽

Treatment Group ◽

Cancer Progression ◽

Messenger Rna ◽

Noncoding Rna ◽

Mirna Targets ◽

Kaplan Meier ◽

Dmso Treatment ◽

Human Protein Atlas ◽

Kaplan Meier Plotter

Introduction. Baicalein has been shown to have antitumor activities in several cancer types. However, its acting mechanisms remain to be further investigated. This work is aimed at exploring the functional long noncoding RNA (lncRNA)/microRNA (miRNA)/messenger RNA (mRNA) triplets in response to baicalein in hepatocellular carcinoma (HCC) cell to understand the mechanisms of baicalein in HCC. Methods. Differentially expressed lncRNAs (DELs) and miRNAs (DEMs) in HCC cell treated with baicalein were first screened using GSE95504 and GSE85511, respectively. miRNA targets for DELs were predicted and intersected with DEMs, after which the miRNA expression was validated using ENCORI and its prognostic value was assessed using Kaplan-Meier plotter. Potential miRNA targets were predicted by 3 prediction tools, after which expression level was validated at UALCAN and Human Protein Atlas. Kaplan-Meier plotter was used to evaluate the effects of these genes on overall survival and recurrence-free survival of HCC patients. Enrichment analyses for these genes were performed at DAVID. Results. Here, we identified 14 overlapping DELs and 26 overlapping DEMs in the baicalein treatment group than those in the DMSO treatment group. Subsequently, by analyzing expression and clinical significance of miRNAs, hsa-miR-4443 was found as a highly potential miRNA target. Then, targets of hsa-miR-4443 were predicted and analyzed, and we found AKT1 was the most potential target for hsa-miR-4443. Hence, the lncRNAs-hsa-miR-4443-AKT1 axis that can respond to baicalein was established. Conclusion. Collectively, we elucidated a role of lncRNAs-hsa-miR-4443-AKT1 pathway in response to baicalein treatment in HCC, which could help us understand the roles of baicalein in inhibiting cancer progression and may provide novel insights into the mechanisms behind HCC progression.

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Up-regulated RFC2 Predicts Unfavorably Progression in Hepatocellular Carcinoma

10.21203/rs.3.rs-72856/v1 ◽

2020 ◽

Author(s):

Zaixiong Ji ◽

Jiaqi Li ◽

Jianbo Wang

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cancer ◽

Tumor Grade ◽

Replication Factor C ◽

Ppi Network ◽

Protein Protein Interaction ◽

Kaplan Meier ◽

Human Protein Atlas ◽

Factor C ◽

Kaplan Meier Plotter

Abstract Background: Replication factor C (RFC) is closely related to tumor progression and metastasis. However, the functional significance of RFC2 in hepatocellular carcinoma remains unclear.Materials and methods: In order to solve this problem, the expression of RFC2 in liver cancer patients was analyzed through ONCOMINE, UALCAN, human protein atlas. Survival analysis was conducted using Kaplan-Meier plotter and GEPIA. GO and KEGG enrichment analyses were carried out. The protein-protein interaction (PPI) network was performed through Metascape.Result: The transcription and protein level of RFC2 in HCC were overexpressed, which was significantly related to the clinical individual cancer stage and pathological tumor grade of HCC patients. In addition, in patients with liver cancer, higher RFC2 expression was found to be significantly correlated with shorter OS and DFS. Furthermore, the function of RFC2 in liver cancer was DNA replication, and its main mechanism was the phase transition of the cell cycle.Conclusion: RFC2 might promote the development of liver cancer. It could also be used as a novel biomarker for the prognosis of liver cancer.

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Comprehensive Analysis of the Prognosis for Chemokine-Like Factor MARVEL Transmembrane Domain-Containing Family in Hepatocellular Carcinoma

10.21203/rs.3.rs-749291/v1 ◽

2021 ◽

Author(s):

Dan Li ◽

Shenglan Huang ◽

Liying Sun ◽

Jianbing Wu

Keyword(s):

Hepatocellular Carcinoma ◽

Transmembrane Domain ◽

Mrna Level ◽

Family Members ◽

Tumor Development ◽

Progression Free Survival ◽

Kaplan Meier ◽

Tcga Dataset ◽

Cox Analysis ◽

Kaplan Meier Plotter

Abstract Background and Purpose: Chemokine-like factor (CKLF) MARVEL transmembrane domain-containing family (CMTMs), including chemokine-like factor (CKLF) and CMTM1 to CMTM8. All of these genes participate in tumor development and metastasis of hepatocellular carcinoma (HCC). However, prognosis values and the distinct roles of different CMTMs in HCC are still un-clarified.Materials and Methods: To address this issue, the study explored the function of CMTM family members in the prognosis of HCC by TCGA dataset, UALCAN, Kaplan-Meier Plotter, MethSurv, TIMER2.0 databases.Results: The CKLF and CMTM1/3/4/7/8 mRNA expression was obviously elevated in HCC tissues, while CMTM2/5/6 was lowly expressed. Besides, the mRNA level of CMTMs was closely linked to cancer stage, node metastasis status and tumor grades in HCC patients. What’s more, the expression of CMTM2/5 was correlated with favorable overall survival (OS), while high expressions CKLF and CMTM1/7 were associated with poor OS. Simultaneously, low CKLF and CMTM1/4/7 expressions were significantly relevant to better progression-free survival (PFS), while low CMTM5 expression was apparently concerned with worse PFS. In DNA methylation level, 47 CpGs of CMTMs displayed markedly prognostic values. Multivariate cox analysis also revealed that affecting shorter OS outcomes prognostic factors of CKLF and CMTM7 were independent. GSEA results suggested that CKLF and CMTM7 participated in the development and progression of HCC accompanied with multiple biological processes. Furthermore, CMTMs were dramatically associated with tumor immune infiltrating cells (TIICs) (e.g., neutrophils cells), but CMTM8 expression level was no significant correlations with TIICs.Conclusion: This study renders new insight into the prognostic values of CMTM family members in HCC. Overall, our results indicated that CKLF and CMTM7 could be the prognostic biomarkers in HCC patients.

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CBX3 Is a Prognostic Biomarker That Is Correlated With Lymphocyte Infiltration in Hepatocellular Carcinoma

10.21203/rs.3.rs-835590/v1 ◽

2021 ◽

Author(s):

Jia-Ning Zhang ◽

Qi fei TAO ◽

Dong yang Ding ◽

YUAN YANG ◽

Wei-Ping Zhou

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cancer ◽

Immune Cells ◽

Immune Checkpoint ◽

Bioinformatics Analysis ◽

Immune Cell ◽

Kaplan Meier ◽

Human Protein Atlas ◽

Infiltrating Lymphocytes ◽

Kaplan Meier Plotter

Abstract Background: CBX3 is a key gene that is involved in immune cell regulation, however, its prognostic values and its correlation with infiltrating lymphocytes in various cancers have not been clearly established. This study aims to investigate the role CBX3 in hepatocellular carcinoma (HCC).Methods: We first reviewed the expression of CBX3 in different cancers and adjacent tissues using oncomine database. Next, the authors focus on the expression of CBX3 in hepatocellular carcinoma. Therefore, the expression of CBX3 in hepatocellular carcinoma were analyzed through UALCAN online analysis website and the Human Protein Atlas (www.proteinatlas.org) website. In addition, we further found that CBX3 can be identified as an effective marker for the prognostic guidance of hepatocellular carcinoma according to the Kaplan-Meier plotter database and the Bioinformatics analysis online websites (www.aclbi.com). Next, we used the Bioinformatics analysis online websites to explore whether the expression level of CBX3 in liver cancer is related to the infiltration of certain immune cells. In addition, we also predicted the correlation between immune checkpoint and CBX3 in liver cancer.Results: The analysis results preliminarily show that CBX3 be expressed abnormally in many cancers, and CBX3 was significantly up-regulated in HCC. The high expression of CBX3 indicated survival outcomes and it showed a huge potential as a effective marker for the prognostic guidance of hepatocellular carcinoma. Furthermore, we found that CBX3 in liver cancer is related to the infiltration of certain immune cells, including CD4+ T cells, macrophages and B cells. In addition, the results showed HAVCR2 is most likely to become an effective immune checkpoint for HCC patients immunotherapy with high CBX3 expression.Conclusions: CBX3 is a potential diagnostic and prognostic marker in HCC and related to the infiltration of certain immune cells. It is expected to become a breakthrough point in immunotherapy in the future.

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Comprehensive Analysis of Aldehyde Dehydrogenases (ALDHs) and Its Significant Role in Hepatocellular Carcinoma

Biochemical Genetics ◽

10.1007/s10528-021-10178-0 ◽

2021 ◽

Author(s):

Senbang Yao ◽

Wenjun Chen ◽

He Zuo ◽

Ziran Bi ◽

Xiuqing Zhang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cancer ◽

Oxidative Dna Damage ◽

Tumor Grade ◽

The Cancer Genome Atlas ◽

Kaplan Meier ◽

Human Protein Atlas ◽

Cancer Genome Atlas ◽

The Relationship ◽

Kaplan Meier Plotter

AbstractOxidative DNA damage is closely related to the occurrence and progression of cancer. Oxidative stress plays an important role in alcohol-induced hepatocellular carcinoma (HCC). Aldehyde dehydrogenase (ALDH) is a family of enzymes that plays an essential role in the reducing oxidative damage. However, how ALDHs family affects alcohol-related HCC remains obscure. We aimed to explore the correlation between the differential expression of ALDHs in patients with HCC and pathological features, as well as the relationship between ALDHs and prognosis, and finally analyze the possible mechanism of ALDHs in targeted therapy of HCC. The data of HCC were downloaded from The Cancer Genome Atlas (TCGA) database. This research explored the expression and prognostic values of ALDHs in HCC using Oncomine, UALCAN, Human Protein Atlas, cBioPortal, Kaplan–Meier plotter, GeneMANIA, Tumor Immune Estimation Resource, GEPIA databases, and WebGestalt. Low mRNA and protein expressions of ALDHs were found to be significantly associated with tumor grade and clinical cancer stages in HCC patients. In particular, the loss of ALDH expression is more obvious in Asians, and its effect on prognosis is far more significant than that in the White race. Our findings play an important role in the study of prognostic markers and anti-liver cancer therapeutic targets for the members of the ALDHs family, especially in patients with liver cancer in Asia.

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Bioinformatics Analysis and Insights for The Role of COMMD7 in Hepatocellular Carcinoma

10.21203/rs.3.rs-79438/v1 ◽

2020 ◽

Author(s):

Xuehui Peng ◽

Yonggang He ◽

Xiaobing Huang ◽

Nan You ◽

Huiying Gu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Bioinformatics Analysis ◽

Tissue Expression ◽

The Cancer Genome Atlas ◽

Research Progress ◽

Kaplan Meier ◽

Tumor Tissues ◽

Cancer Genome Atlas ◽

Kaplan Meier Plotter

Abstract Background: The tumorigenesis and development of hepatocellular carcinoma (HCC) is a process involving multiple factors. The COMMDs family proteins were reported to play important roles in various disease and cancers including HCC. We previously found COMMD7 acted as a HCC-promotion factor; however, further understanding on COMMD7 was needed. We conducted these bioinformatics analysis for the purpose of comprehensive understanding of the functional role of COMMD7 in HCC.Methods: The bioinformatics analysis of COMMD7 were launched by online platforms including KEGG, GEPIA, cBioportal, Gene Ontology and The Kaplan-Meier plotter. Data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) were downloaded, and the data analysis and processing were conducted by RStudio (version 1.3.959) software.Results: The expression profile results of COMMD7 in TCGA and GTEx database suggested that COMMD7 expressed highly in liver tumor tissues and positively related with poorer prognosis (p<0.01); COMMD7 also contributed to the early development of HCC as its higher expression resulted in progression from stage I to stage III (p<0.01). Based on our previous studies, COMMD7 may target NF-κB signaling and CXCL10 to enhance the proliferation of hepatoma cells so that promoting the development of HCC. Conclusions：This study updates the current studies about the newly recognized roles of COMMD7 in the progression of HCC, summarizing the research progress and prospects of COMMD7 comprehensively, offering an outlook for the future investigation and targeted therapy of HCC.

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