Transcriptomic identification of HBx-associated hub genes in hepatocellular carcinoma

Background Hepatocellular carcinoma (HCC) is one of the most common malignancies around the world. Among the risk factors involved in liver carcinogenesis, hepatitis B virus (HBV) X protein (HBx) is considered to be a key regulator in hepatocarcinogenesis. Whether HBx promotes or protects against HCC remains controversial, therefore exploring new HBx-associated genes is still important. Methods HBx was overexpressed in HepG2, HepG2.2.15 and SMMC-7721 cell lines, primary mouse hepatocytes and livers of C57BL/6N mice. High-throughput RNA sequencing profiling of HepG2 cells with HBx overexpression and related differentially-expressed genes (DEGs), pathway enrichment analysis, protein-protein interaction networks (PPIs), overlapping analysis were conducted. In addition, Gene Expression Omnibus (GEO) and proteomic datasets of HBV-positive HCC datasets were used to verify the expression and prognosis of selected DEGs. Finally, we also evaluated the known oncogenic role of HBx by oncogenic array analysis. Results A total of 523 DEGs were obtained from HBx-overexpressing HepG2 cells. Twelve DEGs were identified and validated in cells transiently transfected with HBx and three datasets of HBV-positive HCC transcription profiles. In addition, using the Kaplan-Meier plotter database, the expression levels of the twelve different genes were further analyzed to predict patient outcomes. Conclusion Among the 12 identified HBx-associated hub genes, HBV-positive HCC patients expressing ARG1 and TAT showed a good overall survival (OS) and relapse-free survival (RFS). Thus, ARG1 and TAT expression could be potential prognostic markers.

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Three novel circRNAs upregulated in tissue and plasma from hepatocellular carcinoma patients and their regulatory network

Cancer Cell International ◽

10.1186/s12935-021-01762-w ◽

2021 ◽

Vol 21 (1) ◽

Cited By ~ 1

Author(s):

Lianghai Wang ◽

Lisha Zhou ◽

Jun Hou ◽

Jin Meng ◽

Ke Lin ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Regulatory Network ◽

Expression Profiles ◽

Interaction Network ◽

Enrichment Analysis ◽

Circular Rnas ◽

Pathway Enrichment Analysis ◽

Plasma Samples ◽

Hub Genes ◽

Protein Protein Interaction

Abstract Background The regulatory roles of circular RNAs (circRNAs) in tumorigenesis have attracted increasing attention. However, novel circRNAs with the potential to be used as serum/plasma biomarkers and their regulatory mechanism in the pathogenesis of hepatocellular carcinoma (HCC) remain explored. Methods CircRNA expression profiles of tumor tissues and plasma samples from HCC patients were compiled and jointly analyzed. CircRNA–miRNA–mRNA interactions were predicted by bioinformatics tools. The expression of interacting miRNAs and mRNA was verified in independent datasets. Survival analysis and pathway enrichment analysis were conducted on hub genes. Results We identified three significantly up-regulated circRNAs (hsa_circ_0009910, hsa_circ_0049783, and hsa_circ_0089172) both in HCC tissues and plasma samples. Two of them were validated to be indeed circular and could be excreted from hepatoma cells. We further revealed four miRNAs (hsa-miR-455-5p, hsa-miR-615-3p, hsa-miR-18a-3p, hsa-miR-4524a-3p) that targeting circRNAs and expressed in human HCC samples, and 95 mRNAs targeted by miRNAs and significantly up-regulated in two HCC cohorts. A protein-protein interaction network revealed 19 hub genes, 12 of them (MCM6, CCNB1, CDC20, NDC80, ZWINT, ASPM, CENPU, MCM3, MCM5, ECT2, CDC7, and DLGAP5) were associated with reduced survival in two HCC cohorts. KEGG, Reactome, and Wikipathway enrichment analysis indicated that the hub genes mainly functioned in DNA replication and cell cycle. Conclusions Our study uncovers three novel deregulated circRNAs in tumor and plasma from HCC patients and provides an insight into the pathogenesis from the circRNA–miRNA–mRNA regulatory network.

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Feature selection with the Fisher score followed by the Maximal Clique Centrality algorithm can accurately identify the hub genes of hepatocellular carcinoma

Scientific Reports ◽

10.1038/s41598-019-53471-0 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Chengzhang Li ◽

Jiucheng Xu

Keyword(s):

Hepatocellular Carcinoma ◽

Random Forest ◽

Interaction Network ◽

Enrichment Analysis ◽

Maximal Clique ◽

Gene Set Enrichment Analysis ◽

Hub Genes ◽

Fisher Score ◽

Protein Protein Interaction ◽

Kaplan Meier

AbstractThis study aimed to select the feature genes of hepatocellular carcinoma (HCC) with the Fisher score algorithm and to identify hub genes with the Maximal Clique Centrality (MCC) algorithm. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed to examine the enrichment of terms. Gene set enrichment analysis (GSEA) was used to identify the classes of genes that are overrepresented. Following the construction of a protein-protein interaction network with the feature genes, hub genes were identified with the MCC algorithm. The Kaplan–Meier plotter was utilized to assess the prognosis of patients based on expression of the hub genes. The feature genes were closely associated with cancer and the cell cycle, as revealed by GO, KEGG and GSEA enrichment analyses. Survival analysis showed that the overexpression of the Fisher score–selected hub genes was associated with decreased survival time (P < 0.05). Weighted gene co-expression network analysis (WGCNA), Lasso, ReliefF and random forest were used for comparison with the Fisher score algorithm. The comparison among these approaches showed that the Fisher score algorithm is superior to the Lasso and ReliefF algorithms in terms of hub gene identification and has similar performance to the WGCNA and random forest algorithms. Our results demonstrated that the Fisher score followed by the application of the MCC algorithm can accurately identify hub genes in HCC.

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Prognostic values and prospective pathway signaling of MicroRNA-182 in ovarian cancer: a study based on gene expression omnibus (GEO) and bioinformatics analysis

Journal of Ovarian Research ◽

10.1186/s13048-019-0580-7 ◽

2019 ◽

Vol 12 (1) ◽

Author(s):

Yaowei Li ◽

Li Li

Keyword(s):

Gene Expression ◽

Target Genes ◽

Gynecological Cancer ◽

Enrichment Analysis ◽

Gene Expression Omnibus ◽

Receptor Interaction ◽

Pathway Enrichment Analysis ◽

Ppi Network ◽

Hub Genes ◽

Protein Protein Interaction

Abstract Background Ovarian carcinoma (OC) is a common cause of death among women with gynecological cancer. MicroRNAs (miRNAs) are believed to have vital roles in tumorigenesis of OC. Although miRNAs are broadly recognized in OC, the role of has-miR-182-5p (miR-182) in OC is still not fully elucidated. Methods We evaluated the significance of miR-182 expression in OC by using analysis of a public dataset from the Gene Expression Omnibus (GEO) database and a literature review. Furthermore, we downloaded three mRNA datasets of OC and normal ovarian tissues (NOTs), GSE14407, GSE18520 and GSE36668, from GEO to identify differentially expressed genes (DEGs). Then the targeted genes of hsa-miR-182-5p (TG_miRNA-182-5p) were predicted using miRWALK3.0. Subsequently, we analyzed the gene overlaps integrated between DEGs in OC and predicted target genes of miR-182 by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. STRING and Cytoscape were used to construct a protein-protein interaction (PPI) network and the prognostic effects of the hub genes were analyzed. Results A common pattern of up-regulation for miR-182 in OC was found in our review of the literature. A total of 268 DEGs, both OC-related and miR-182-related, were identified, of which 133 genes were discovered from the PPI network. A number of DEGs were enriched in extracellular matrix organization, pathways in cancer, focal adhesion, and ECM-receptor interaction. Two hub genes, MCM3 and GINS2, were significantly associated with worse overall survival of patients with OC. Furthermore, we identified covert miR-182-related genes that might participate in OC by network analysis, such as DCN, AKT3, and TIMP2. The expressions of these genes were all down-regulated and negatively correlated with miR-182 in OC. Conclusions Our study suggests that miR-182 is essential for the biological progression of OC.

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BPI and KIR6.1 as significant hub genes for vein graft restenosis

Journal of International Medical Research ◽

10.1177/0300060520969331 ◽

2020 ◽

Vol 48 (11) ◽

pp. 030006052096933

Author(s):

Yun-peng Bai ◽

Bo-chen Yao ◽

Mei Wang ◽

Xian-kun Liu ◽

Xiao-long Zhu ◽

...

Keyword(s):

Vein Graft ◽

Area Under The Curve ◽

Interaction Network ◽

Enrichment Analysis ◽

Gene Expression Omnibus ◽

Differentially Expressed ◽

Control Group ◽

Pathway Enrichment Analysis ◽

Hub Genes ◽

Protein Protein Interaction

Background Vein graft restenosis (VGR), which appears to be caused by dyslipidemia following vascular transplantation, seriously affects the prognosis and long-term quality of life of patients. Methods This study analyzed the genetic data of restenosis (VGR group) and non-stenosis (control group) vessels from patients with coronary heart disease post-vascular transplantation and identified hub genes that might be responsible for its occurrence. GSE110398 was downloaded from the Gene Expression Omnibus database. A repeatability test for the GSE110398 dataset was performed using R language. This included the identification of differentially expressed genes (DEGs), enrichment analysis via Metascape software, pathway enrichment analysis, and construction of a protein–protein interaction network and a hub gene network. Results Twenty-four DEGs were identified between VGR and control groups. The four most important hub genes ( KIR6.1, PCLP1, EDNRB, and BPI) were identified, and Pearson’s correlation coefficient showed that KIR6.1 and BPI were significantly correlated with VGR. KIR6.1 could also sensitively predict VGR (0.9 < area under the curve ≤1). Conclusion BPI and KIR6.1 were differentially expressed in vessels with and without stenosis after vascular transplantation, suggesting that these genes or their encoded proteins may be involved in the occurrence of VGR.

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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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MFGE8, ALB, APOB, APOE, SAA1, A2M, and C3 as Novel Biomarkers for Stress Cardiomyopathy

Cardiovascular Therapeutics ◽

10.1155/2020/1615826 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Xiao-Yu Pan ◽

Zai-Wei Zhang

Keyword(s):

Enrichment Analysis ◽

Gene Expression Omnibus ◽

Left Ventricular ◽

Stress Cardiomyopathy ◽

Receptor Interaction ◽

Pathway Enrichment Analysis ◽

Hub Genes ◽

Protein Protein Interaction ◽

Coronary Syndrome ◽

Extracellular Region

Background. Stress cardiomyopathy (SCM) is a transient reversible left ventricular dysfunction that more often occurs in women. Symptoms of SCM patients are similar to those of acute coronary syndrome (ACS), but little is known about biomarkers. The goals of this study were to identify the potentially crucial genes and pathways associated with SCM. Methods. We analyzed microarray datasets GSE95368 derived from the Gene Expression Omnibus (GEO) database. Firstly, identify the differentially expressed genes (DEGs) between SCM patients in normal patients. Then, the DEGs were used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Finally, the protein-protein interaction (PPI) network was constructed and Cytoscape was used to find the key genes. Results. In total, 25 DEGs were identified, including 10 upregulated genes and 15 downregulated genes. These DEGs were mainly enriched in ECM-receptor interaction, dilated cardiomyopathy (DCM), human papillomavirus infection, and focal adhesion, whereas in GO function classification, they were mainly enriched in the extracellular region, positive regulation of the multicellular organismal process, establishment of localization, and intracellular vesicle. Conclusion. Seven hub genes contained APOE, MFGE8, ALB, APOB, SAA1, A2M, and C3 identified as hub genes of SCM, which might be used as diagnostic biomarkers or molecular targets for the treatment of SCM.

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Identification of potential hub genes associated with the pathogenesis and prognosis of hepatocellular carcinoma via integrated bioinformatics analysis

Journal of International Medical Research ◽

10.1177/0300060520910019 ◽

2020 ◽

Vol 48 (7) ◽

pp. 030006052091001

Author(s):

Ziqi Meng ◽

Jiarui Wu ◽

Xinkui Liu ◽

Wei Zhou ◽

Mengwei Ni ◽

...

Keyword(s):

Gene Expression ◽

Hepatocellular Carcinoma ◽

Interaction Network ◽

Gene Expression Omnibus ◽

Molecular Therapy ◽

Integrated Analysis ◽

Hub Genes ◽

Protein Protein Interaction ◽

Interactive Analysis ◽

Kaplan Meier

Objective The objective was to identify potential hub genes associated with the pathogenesis and prognosis of hepatocellular carcinoma (HCC). Methods Gene expression profile datasets were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between HCC and normal samples were identified via an integrated analysis. A protein–protein interaction network was constructed and analyzed using the STRING database and Cytoscape software, and enrichment analyses were carried out through DAVID. Gene Expression Profiling Interactive Analysis and Kaplan–Meier plotter were used to determine expression and prognostic values of hub genes. Results We identified 11 hub genes ( CDK1, CCNB2, CDC20, CCNB1, TOP2A, CCNA2, MELK, PBK, TPX2, KIF20A, and AURKA) that might be closely related to the pathogenesis and prognosis of HCC. Enrichment analyses indicated that the DEGs were significantly enriched in metabolism-associated pathways, and hub genes and module 1 were highly associated with cell cycle pathway. Conclusions In this study, we identified key genes of HCC, which indicated directions for further research into diagnostic and prognostic biomarkers that could facilitate targeted molecular therapy for HCC.

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Analysis of differential gene expression between right-sided and left-sided colon cancer by bioinformatics analysis

10.21203/rs.3.rs-23894/v1 ◽

2020 ◽

Author(s):

Qiangwei Chi ◽

Shizuan Chen ◽

Shaotang Li

Keyword(s):

Gene Expression ◽

Colon Cancer ◽

Bioinformatics Analysis ◽

Disease Free Survival ◽

Enrichment Analysis ◽

Gene Expression Omnibus ◽

Pathway Enrichment Analysis ◽

Hub Genes ◽

Protein Protein Interaction ◽

Ppi Networks

Abstract Background Colon cancer is a common tumor of the digestive tract worldwide. Recent researches have revealed that colon cancer exhibits distinct differences in clinical and biological characteristics depending on the location of the tumor. However, the underlying genetic and molecular mechanism of the differences between right-sided colon cancer (RCC) and left-sided colon cancer (LCC) are not fully understood. This study aimed to identify molecular potential biomarkers and therapeutic targets for precise treatment of right-sided and left-sided colon cancer using bioinformatics analysis. Methods The gene microarray profile, named GSE44076, from the Gene Expression Omnibus (GEO) public database was downloaded and processed to then select differentially expressed genes (DEGs) on the base of two sample groups of RCC and LCC. Also, gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, protein–protein interaction (PPI) network construction, module analysis, validation of hub genes, and survival analysis. Results Finally, we obtained 2259 DEGs between RCC and LCC, 1300 of which were upregulated in RCC and 945 of which were upregulated in LCC. The results of GO and KEGG analysis of the DEGs indicated that the biological functions of DEGs in RCC and LCC were significantly different. CTLA4, IL10, IL2RB, IFNG, NCAM1, EGFR, MYC, SRC, CUL3, and NCBP2 were identified from the PPI networks as the hub genes of RCC and LCC. Among the hub genes, the log-rank tests for overall survival (OS) and disease free survival (DFS) were applied. Moreover, all hub genes, except CUL3, had differential expression levels of miRNA between tumor group and normal group. Conclusion These hub genes and pathways identified based on bioinformatics analysis might conduce to explain the differences between RCC and LCC, and most of the hub genes were specific to the malignant tissues. Notably, these hub genes, especially the genes associated with immunotherapy such as CTLA4, might be potential specific targets or prognostic markers for precise treatment of colon cancer.

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Identification of Key Genes and miRNAs in Osteosarcoma Patients with Chemoresistance by Bioinformatics Analysis

BioMed Research International ◽

10.1155/2018/4761064 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 9

Author(s):

Binbin Xie ◽

Yiran Li ◽

Rongjie Zhao ◽

Yuzi Xu ◽

Yuhui Wu ◽

...

Keyword(s):

Enrichment Analysis ◽

Gene Expression Omnibus ◽

Differentially Expressed ◽

Pathway Enrichment Analysis ◽

Regulation Of Transcription ◽

Functional Annotations ◽

Protein Protein Interaction ◽

Ppi Networks ◽

Search Tool ◽

Poor Outcomes

Chemoresistance is a significant factor associated with poor outcomes of osteosarcoma patients. The present study aims to identify Chemoresistance-regulated gene signatures and microRNAs (miRNAs) in Gene Expression Omnibus (GEO) database. The results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) included positive regulation of transcription, DNA-templated, tryptophan metabolism, and the like. Then differentially expressed genes (DEGs) were uploaded to Search Tool for the Retrieval of Interacting Genes (STRING) to construct protein-protein interaction (PPI) networks, and 9 hub genes were screened, such as fucosyltransferase 3 (Lewis blood group) (FUT3) whose expression in chemoresistant samples was high, but with a better prognosis in osteosarcoma patients. Furthermore, the connection between DEGs and differentially expressed miRNAs (DEMs) was explored. GEO2R was utilized to screen out DEGs and DEMs. A total of 668 DEGs and 5 DEMs were extracted from GSE7437 and GSE30934 differentiating samples of poor and good chemotherapy reaction patients. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used to perform GO and KEGG pathway enrichment analysis to identify potential pathways and functional annotations linked with osteosarcoma chemoresistance. The present study may provide a deeper understanding about regulatory genes of osteosarcoma chemoresistance and identify potential therapeutic targets for osteosarcoma.

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Identification of Key miRNAs in the Treatment of Dabrafenib-Resistant Melanoma

BioMed Research International ◽

10.1155/2021/5524486 ◽

2021 ◽

Vol 2021 ◽

pp. 1-14

Author(s):

Guangyu Gao ◽

Zhen Yao ◽

Jiaofeng Shen ◽

Yulong Liu

Keyword(s):

Drug Resistance ◽

Molecular Mechanism ◽

Target Genes ◽

Enrichment Analysis ◽

Gene Expression Omnibus ◽

The Cancer Genome Atlas ◽

Pathway Enrichment Analysis ◽

Ppi Network ◽

Protein Protein Interaction ◽

Obvious Association

Dabrafenib resistance is a significant problem in melanoma, and its underlying molecular mechanism is still unclear. The purpose of this study is to research the molecular mechanism of drug resistance of dabrafenib and to explore the key genes and pathways that mediate drug resistance in melanoma. GSE117666 was downloaded from the Gene Expression Omnibus (GEO) database and 492 melanoma statistics were also downloaded from The Cancer Genome Atlas (TCGA) database. Besides, differentially expressed miRNAs (DEMs) were identified by taking advantage of the R software and GEO2R. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) and FunRich was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to identify potential pathways and functional annotations linked with melanoma chemoresistance. 9 DEMs and 872 mRNAs were selected after filtering. Then, target genes were uploaded to Metascape to construct protein-protein interaction (PPI) network. Also, 6 hub mRNAs were screened after performing the PPI network. Furthermore, a total of 4 out of 9 miRNAs had an obvious association with the survival rate ( P < 0.05 ) and showed a good power of risk prediction model of over survival. The present research may provide a deeper understanding of regulatory genes of dabrafenib resistance in melanoma.

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