scholarly journals Bioinformatics analysis of different candidate genes involved in hepatocellular carcinoma induced by HepG2 cells or tumor cells of patients

2020 ◽  
Vol 48 (6) ◽  
pp. 030006052093211
Author(s):  
Xiang Zhang ◽  
Songna Yin ◽  
Ke Ma

Objective Hepatocellular carcinoma (HCC) is a common cancer with a high mortality rate; the molecular mechanism involved in HCC remain unclear. We aimed to provide insight into HCC induced with HepG2 cells and identify genes and pathways associated with HCC, as well as potential therapeutic targets. Methods Dataset GSE72581 was downloaded from the Gene Expression Omnibus, including samples from mice injected in liver parenchyma with HepG2 cells, and from mice injected with cells from patient tumor explants. Differentially expressed genes (DEGs) between the two groups of mice were analyzed. Then, gene ontology and Kyoto Encyclopedia of Gene and Genomes pathway enrichment analyses were performed. The MCODE plug-in in Cytoscape was applied to create a protein–protein interaction (PPI) network of DEGs. Results We identified 1,405 DEGs (479 upregulated and 926 downregulated genes), which were enriched in complement and coagulation cascades, peroxisome proliferator-activated receptor signaling pathway, and extracellular matrix–receptor interaction. The top 4 modules and top 20 hub genes were identified from the PPI network, and associations with overall survival were determined using Kaplan–Meier analysis. Conclusion This preclinical study provided data on molecular targets in HCC that could be useful in the clinical treatment of HCC.

2020 ◽  
Vol 2020 ◽  
pp. 1-16 ◽  
Author(s):  
Yiting Tian ◽  
Yang Xing ◽  
Zheng Zhang ◽  
Rui Peng ◽  
Luyu Zhang ◽  
...  

Gastric cancer (GC) is one of the most common malignancies in the world, with morbidity and mortality ranking second among all cancers. Accumulating evidences indicate that circular RNAs (circRNAs) are closely correlated with tumorigenesis. However, the mechanisms of circRNAs still remain unclear. This study is aimed at determining hub genes and circRNAs and analyzing their potential biological functions in GC. Expression profiles of mRNAs and circRNAs were downloaded from the Gene Expression Omnibus (GEO) data sets of GC and paracancer tissues. Differentially expressed genes (DEGs) and differentially expressed circRNAs (DE-circRNAs) were identified. The target miRNAs of DE-circRNAs and the bidirectional interaction between target miRNAs and DEGs were predicted. Functional analysis was performed, and the protein-protein interaction (PPI) network and the circRNA-miRNA-mRNA network were established. A total of 456 DEGs and 2 DE-circRNAs were identified with 3 mRNA expression profiles and 2 circRNA expression profiles. GO analysis indicated that DEGs were mainly enriched in extracellular matrix and cell adhesion, and KEGG confirmed that DEGs were mainly associated with focal adhesion, the PI3K-Akt signaling pathway, extracellular matrix- (ECM)- receptor interaction, and gastric acid secretion. 15 hub DEGs (BGN, COL1A1, COL1A2, FBN1, FN1, SPARC, SPP1, TIMP1, UBE2C, CCNB1, CD44, CXCL8, COL3A1, COL5A2, and THBS1) were identified from the PPI network. Furthermore, the survival analysis indicate that GC patients with a high expression of the following 9 hub DEGs, namely, BGN, COL1A1, COL1A2, FBN1, FN1, SPARC, SPP1, TIMP1, and UBE2C, had significantly worse overall survival. The circRNA-miRNA-mRNA network was constructed based on 1 circRNA, 15 miRNAs, and 45 DEGs. In addition, the 45 DEGs included 5 hub DEGs. These results suggested that hub DEGs and circRNAs could be implicated in the pathogenesis and development of GC. Our findings provide novel evidence on the circRNA-miRNA-mRNA network and lay the foundation for future research of circRNAs in GC.


Dose-Response ◽  
2020 ◽  
Vol 18 (1) ◽  
pp. 155932582090753
Author(s):  
Tianlong Wu ◽  
Honghai Cao ◽  
Lei Liu ◽  
Kan Peng

Background: The risk of malignant transformation of enchondromas (EC) toward central chondrosarcoma is increased up to 35%, while the exact etiology of EC is unknown. The purpose of this research was to authenticate gene signatures during EC and reveal their potential mechanisms in occurrence and development of EC. Methods: The gene expression profiles was acquired from Gene Expression Omnibus database (no. GSE22855). The gene ontology (GO), protein–protein interaction (PPI) network and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were utilized to identify differentially expressed genes (DEGs). Results: Finally, 242 DEGs were appraisal, containing 200 overregulated genes and 42 downregulated genes. The outcomes of GO analysis indicated that upregulated DEGs were mainly enriched in several biological processes containing response to hypoxia, calcium ion, and negative regulation extrinsic apoptotic signaling pathway. Furthermore, the upregulated DEGs were enriched in extracellular matrix (ECM)–receptor interaction, protein processing in endoplasmic reticulum and ribosome, which was analyzed by KEGG pathway. From the PPI network, the top 10 hub genes were identified, which were related to significant pathways containing ribosome, protein processing in endoplasmic reticulum, and ECM-receptor interaction. Conclusion: In conclusion, the present study may be helpful for understanding the diagnostic biomarkers of EC.


2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Yaowei Li ◽  
Li Li

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.


PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12697
Author(s):  
Zhengzhong Ni ◽  
Jun Lu ◽  
Weiyi Huang ◽  
Hanif Khan ◽  
Xuejun Wu ◽  
...  

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.


2019 ◽  
Author(s):  
Sepideh Dashti ◽  
Soudeh Ghafouri-Fard

Abstract Backgrounds Breast cancer is a highly heterogeneous disorder characterized by dysregulation of expression of numerous genes and cascades. The conventional pathologic classification of breast cancer is not sufficient for the prediction of breast cancer behavior and response to therapy.Methods We have retrieved data of two microarray datasets (GSE65194 and GSE45827) from the NCBI Gene Expression Omnibus database (GEO). R package was used for identification of differentially expressed genes (DEGs), assessment of gene ontology (GO) and pathway enrichment evaluation. The DEGs were integrated to construct a protein-protein interaction (PPI) network. Next, hub genes were recognized using the Cytoscape software and lncRNA-mRNA co-expression analysis was performed to evaluate the potential roles of lncRNAs. The interactive information among DEGs and the PPI network was obtained using the STRING online database. Finally, the clinical importance of the obtained genes was assessed using Kaplan-Meier survival analysis.Results After excluding the outliers from the GSE65194 and GSE45827 datasets and data normalization, 866 DEGs including 712 upregulated and 154 downregulated DEGs were detected between breast cancer and normal samples. Up-regulated DEGs were enriched in six pathways including ‘Cell cycle’, ‘Oocyte meiosis’ and ‘Focal adhesion’. Down-regulated DEGs were enriched in five pathways including ‘Peroxisome-proliferator-activated receptors (PPAR) signaling pathway’, ‘Metabolism of xenobiotics by cytochrome P450’, ‘Adipocytokine signaling pathway’ and ‘Cytokine-cytokine receptor interaction’ pathways. CCNA2, CDK1, MAD2L1, and CCNB2 were significantly enriched in several biological pathways. These four genes showed strong expression in breast cancer samples as compared to normal breast tissue. We also identified 12 lncRNAs with a significant correlation with MAD2L1 and CCNB2 genes. MAD2L1, CCNA2, RAD51-AS1, and LINC01089 have the most prediction potential among all candidate hub genes.Conclusion Our study offers a framework for recognition of the mRNA-lncRNA network in breast cancer and the detection of important pathways that could be used as therapeutic targets in this kind of cancer.


2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Weishuang Xue ◽  
Jinwei Li ◽  
Kailei Fu ◽  
Weiyu Teng

Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disease that affects the quality of life of elderly individuals, while the pathogenesis of AD is still unclear. Based on the bioinformatics analysis of differentially expressed genes (DEGs) in peripheral blood samples, we investigated genes related to mild cognitive impairment (MCI), AD, and late-stage AD that might be used for predicting the conversions. Methods. We obtained the DEGs in MCI, AD, and advanced AD patients from the Gene Expression Omnibus (GEO) database. A Venn diagram was used to identify the intersecting genes. Gene Ontology (GO) and Kyoto Gene and Genomic Encyclopedia (KEGG) were used to analyze the functions and pathways of the intersecting genes. Protein-protein interaction (PPI) networks were constructed to visualize the network of the proteins coded by the related genes. Hub genes were selected based on the PPI network. Results. Bioinformatics analysis indicated that there were 61 DEGs in both the MCI and AD groups and 27 the same DEGs among the three groups. Using GO and KEGG analyses, we found that these genes were related to the function of mitochondria and ribosome. Hub genes were determined by bioinformatics software based on the PPI network. Conclusions. Mitochondrial and ribosomal dysfunction in peripheral blood may be early signs in AD patients and related to the disease progression. The identified hub genes may provide the possibility for predicting AD progression or be the possible targets for treatments.


2022 ◽  
Vol 12 (3) ◽  
pp. 523-532
Author(s):  
Xin Yan ◽  
Chunfeng Liang ◽  
Xinghuan Liang ◽  
Li Li ◽  
Zhenxing Huang ◽  
...  

<sec> <title>Objective:</title> This study aimed to identify the potential key genes associated with the progression and prognosis of adrenocortical carcinoma (ACC). </sec> <sec> <title>Methods:</title> Differentially expressed genes (DEGs) in ACC cells and normal adrenocortical cells were assessed by microarray from the Gene Expression Omnibus database. The biological functions of the classified DEGs were examined by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses and a protein–protein interaction (PPI) network was mapped using Cytoscape software. MCODE software was also used for the module analysis and then 4 algorithms of cytohubba software were used to screen hub genes. The overall survival (OS) examination of the hub genes was then performed by the ualcan online tool. </sec> <sec> <title>Results:</title> Two GSEs (GSE12368, GSE33371) were downloaded from GEO including 18 and 43 cases, respectively. One hundred and sixty-nine DEGs were identified, including 57 upregulated genes and 112 downregulated genes. The Gene Ontology (GO) analyses showed that the upregulated genes were significantly enriched in the mitotic cytokines is, nucleus and ATP binding, while the downregulated genes were involved in the positive regulation of cardiac muscle contraction, extracellular space, and heparin-binding (P < 0.05). The Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) pathway examination showed significant pathways including the cell cycle and the complement and coagulation cascades. The protein– protein interaction (PPI) network consisted of 162 nodes and 847 edges, including mitotic nuclear division, cytoplasmic, protein kinase binding, and cell cycle. All 4 identified hub genes (FOXM1, UBE2C, KIF11, and NDC80) were associated with the prognosis of adrenocortical carcinoma (ACC) by survival analysis. </sec> <sec> <title>Conclusions:</title> The present study offered insights into the molecular mechanism of adrenocortical carcinoma (ACC) that may be beneficial in further analyses. </sec>


2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Guangyu Gao ◽  
Zhen Yao ◽  
Jiaofeng Shen ◽  
Yulong Liu

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.


2021 ◽  
Author(s):  
Q Shi ◽  
Z Meng ◽  
XX Tian ◽  
YF Wang ◽  
WH Wang

Aims: We aim to provide new insights into the mechanisms of hepatocellular carcinoma (HCC) and identify key genes as biomarkers for the prognosis of HCC. Materials & methods: Differentially expressed genes between HCC tissues and normal tissues were identified via the Gene Expression Omnibus tool. The top ten hub genes screened by the degree of the protein nodes in the protein–protein interaction network also showed significant associations with overall survival in HCC patients. Results: A prognostic model containing a five-gene signature was constructed to predict the prognosis of HCC via multivariate Cox regression analysis. Conclusion: This study identified a novel five-gene signature ( CDK1, CCNB1, CCNB2, BUB1 and KIF11) as a significant independent prognostic factor.


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