scholarly journals Up-regulated RFC2 Predicts Unfavorably Progression in Hepatocellular Carcinoma

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.

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

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.

scholarly journals Up-regulated RFC2 predicts unfavorable progression in hepatocellular carcinoma

Hereditas ◽  
2021 ◽  
Vol 158 (1) ◽  
Author(s):  
Zaixiong Ji ◽  
Jiaqi Li ◽  
Jianbo Wang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Dna Replication ◽  
Liver Cancer ◽  
Tumor Grade ◽  
Cell Counting ◽  
Protein Protein Interaction ◽  
And Migration ◽  
Factor C ◽  
Proliferation And Migration

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. Western blotting, cell counting kit-8 and transwell assay were used to detect the effect of RFC2 on cell proliferation and migration. Results 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. Biological experiments demonstrated that knockdown of RFC2 reduced the proliferation and migration of HCC cells. Conclusion RFC2 might promote the development of liver cancer, which might be achieved by regulating cell cycle and DNA replication. It could be used as a novel biomarker for the prognosis of liver cancer.

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

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.

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

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.

scholarly journals Expression and prognostic roles of PRDXs gene family in hepatocellular carcinoma

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Mingxing Xu ◽  
Jianliang Xu ◽  
Dun Zhu ◽  
Rishun Su ◽  
Baoding Zhuang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Acid Metabolism ◽  
Family Members ◽  
Interaction Network ◽  
Genetic Alterations ◽  
Database Analysis ◽  
Kaplan Meier ◽  
Canonical Pathways ◽  
Human Protein Atlas ◽  
Kaplan Meier Plotter

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.

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

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.

scholarly journals Systematic Elucidation of the Mechanism of Quercetin against Gastric Cancer via Network Pharmacology Approach

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Liangjun Yang ◽  
Zhipeng Hu ◽  
Jiajie Zhu ◽  
Qiting Liang ◽  
Hengli Zhou ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Molecular Docking ◽  
Network Pharmacology ◽  
Ppi Network ◽  
Online Tool ◽  
Protein Protein Interaction ◽  
Kaplan Meier ◽  
Novel Approach ◽  
Therapeutic Mechanisms ◽  
Kaplan Meier Plotter

This study was aimed at elucidating the potential mechanisms of quercetin in the treatment of gastric cancer (GC). A network pharmacology approach was used to analyze the targets and pathways of quercetin in treating GC. The predicted targets of quercetin against GC were obtained through database mining, and the correlation of these targets with GC was analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Next, the protein-protein interaction (PPI) network was constructed, and overall survival (OS) analysis of hub targets was performed using the Kaplan–Meier Plotter online tool. Finally, the mechanism was further analyzed via molecular docking of quercetin with the hub targets. Thirty-six quercetin-related genes were identified, 15 of which overlapped with GC-related targets. These targets were further mapped to 319 GO biological process terms and 10 remarkable pathways. In the PPI network analysis, six hub targets were identified, including AKT1, EGFR, SRC, IGF1R, PTK2, and KDR. The high expression of these targets was related to poor OS in GC patients. Molecular docking analysis confirmed that quercetin can bind to these hub targets. In conclusion, this study provided a novel approach to reveal the therapeutic mechanisms of quercetin on GC, which will ease the future clinical application of quercetin in the treatment of GC.

scholarly journals ITGB2 as a Novel Biomarker Correlating With Prognosis and Immune Infiltrates in Ovarian Cancer

2021 ◽  
Author(s):  
chanyuan li ◽  
Ting Wan ◽  
Ting Deng ◽  
Junya Cao ◽  
He Huang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Protein Interaction ◽  
Ppi Network ◽  
Hub Genes ◽  
Immune Infiltration ◽  
Protein Protein Interaction ◽  
Kaplan Meier ◽  
Kaplan Meier Plotter

Abstract Background: Epithelial ovarian cancer is nowadays one of the malignancies in women, this study aimed to identify novel biomarkers to predict prognosis and immunotherapy efficacy.Methods: The differentially expressed genes (DEGs) obtained from online database Gene Expression Omnibus (GEO)were screened via GEO2R and Venn diagram software, gene enrichment was analysed by Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG), then protein protein interaction(PPI)network and Cytoscape software were used to confirm the genes closely related to ovarian cancer. Survival analysis of hub genes were obtained from Kaplan–Meier plotter, with their differential expression in specimen validated by Gene Expression Profiling Interactive Analysis (GEPIA) and an integrated repository portal for tumor-immune system interactions (TISIDB). Finally, we used the Tumor Immune Estimation Resource 2.0 (TIMER2.0) and application Estimate the Proportion of Immune and Cancer cells (EPIC) to search the immune infiltration characteristics of the genes.Results: 355 DEGs between epithelial ovarian cancer and normal ovarian tissue were screened out. These DEGs were associated with extracellular exosome, bicellular tight junction and cell-cell junction, and remarkably enriched in molecules of cell adhesion and leukocyte transendothelial migration activity. Ten hub genes were identified via protein protein interaction (PPI) network: PTAFR, HLA-DRA, OAS2, OAS3, PTPN6, LYN, VAMP8, IRF6, ITGB2, CD47. Furthermore, the Kaplan–Meier plotter was conducted, overexpression of four genes was positively connected to poor prognosis in ovarian cancer:OAS2, OAS3, ITGB2, CD47,which were also correlated with immune infiltrates in ovarian cancer and had the highest degree of correlation with tumor associated macrophages (TAMs) infiltration, among which ITGB2 was highly correlated with TAMs infiltration level.Conclusion: ITGB2, OAS2, OAS3, and CD47 are upregulated with unfavorable prognosis in ovarian cancer, and ITGB2 may act as a novel prognostic biomarker with immune infiltration values.

scholarly journals CAST as a Potential Oncogene From Machine Searching in Gastric Cancer Infiltrated with Macrophage and Associated with Lgr5

2021 ◽  
Author(s):  
Kuang-Tsu Yang ◽  
Chia-Jung Li ◽  
Renin Chang ◽  
Jui-Tzu Wang ◽  
Yih-Wen Tarng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Macrophage Infiltration ◽  
Clinical Prognosis ◽  
Protein Protein Interaction ◽  
Interactive Analysis ◽  
Kaplan Meier ◽  
Human Protein Atlas ◽  
The Impact ◽  
Kaplan Meier Plotter

Background: Gastric cancer (GC) is one of the leading malignancy diseases worldwide, especially in Asian. CAST is a potential oncogene in GC carcinogenesis process. The character of macrophage infiltration in GC microenvironment was also unaddressed. Methods: We first applied machine searching in gene candidate evaluation of GC. CAST expression was analyzed via the Human Protein Atlas (HPA) and Gene Expression Profiling Interactive Analysis 2 (GEPIA2) database. Protein-protein interaction (PPI) network was downloaded from STRING. We investigated the impact of CAST on clinical prognosis using Kaplan-Meier plotter. The correlations between CAST and Lgr5 and macrophage infiltration in GC was surveyed via TIMER 2.0. Finally, GeneMANIA was also used to evaluate the possible functional linkage between genes. Results: After machine-assisted searching, CAST expression was found signicant difference in the overall survival of GC patients. STRING revealed CAST related proteomics and transcriptomics associations, mainly about CAPN family. Moreover, CAST significantly impacts the prognosis of GC from other datasets validation. Notably, high CAST expression was correlated with worse overall survival in GC patients (hazard ratio = 1.59; logrank P = 9.4 x 10-8). CAST and Lgr5 expressions were both positively correlated with WNT 2 and WNT 2B. Among GC patients in several datasets, CAST and macrophage infiltration evaluated together showed no obvious trend toward poor clinical overall survival. Conclusion: CAST plays an important role in GC clinical prognosis and is associated with WNT 2/WNT 2B/Lgr5. Our study denmostrated that CAST in GC overall survival is regulated by macrophage infiltration.

scholarly journals Expression and Prognostic Roles of PRDXs Gene Family in Hepatocellular Carcinoma

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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