Exploring the Molecular Mechanism and Biomakers of Liver Cancer Based on Gene Expression Microarray.
Ontology highlight
ABSTRACT:
SUBMITTER: Liu P
PROVIDER: S-EPMC4550637 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:: Breast cancer (BRCA) remains the leading cause of cancer morbidity and mortality worldwide. In the present study, we identified novel biomarkers expressed during estradiol and tamoxifen treatment of BRCA. The microarray dataset of E-MTAB-4975 from Array Express database was downloaded, and the differential expressed genes (DEGs) between estradiol-treated BRCA sample and tamoxifen-treated BRCA sample were identified by limma package. The pathway and gene ontology (GO) enrichment analysis, construction of protein-protein interaction (PPI) network, module analysis, construction of target genes-miRNA interaction network and target genes-transcription factor (TF) interaction network were performed using bioinformatics tools. The expression, prognostic values, and mutation of hub genes were validated by SurvExpress database, cBioPortal, and human protein atlas (HPA) database. A total of 856 genes (421 up-regulated genes and 435 down-regulated genes) were identified in T47D (overexpressing Split Ends (SPEN) + estradiol) samples compared to T47D (overexpressing Split Ends (SPEN) + tamoxifen) samples. Pathway and GO enrichment analysis revealed that the DEGs were mainly enriched in response to lysine degradation II (pipecolate pathway), cholesterol biosynthesis pathway, cell cycle pathway, and response to cytokine pathway. DEGs (MCM2, TCF4, OLR1, HSPA5, MAP1LC3B, SQSTM1, NEU1, HIST1H1B, RAD51, RFC3, MCM10, ISG15, TNFRSF10B, GBP2, IGFBP5, SOD2, DHF and MT1H) , which were significantly up- and down-regulated in estradiol and tamoxifen-treated BRCA samples, were selected as hub genes according to the results of protein-protein interaction (PPI) network, module analysis, target genes-miRNA interaction network and target genes-TF interaction network analysis. The SurvExpress database, cBioPortal, and Human Protein Atlas (HPA) database further confirmed that patients with higher expression levels of these hub genes experienced a shorter overall survival. A comprehensive bioinformatics analysis was performed, and potential therapeutic applications of estradiol and tamoxifen were predicted in BRCA samples. The data may unravel the future molecular mechanisms of BRCA.
| S-EPMC6681318 | biostudies-literature
Project description:Esophageal cancer (EC) is one of the most common digestive malignant tumors worldwide. Over the past decades, there have been minimal improvements in outcomes for patients with EC. New targets and novel therapies are needed to improve outcomes for these patients. This study aimed to explore the molecular mechanisms of EC by integrated bioinformatic analyses of the feature genes associated with EC and correlative gene functions which can distinguish cancerous tissues from non-cancerous tissues. Gene expression profile GSE20347 was downloaded from Gene Expression Omnibus (GEO) database, including 17 EC samples and their paired adjacent non-cancerous samples. The differentially expressed genes (DEGs) between EC and normal specimens were identified and then applied to analyze the GO enrichment on gene functions and KEGG pathways. Corresponding Pathway Relation Network (Pathway-net) and Gene Signal Network (signal-net) of DEGs were established based on the data collected from GCBI datasets. The results showed that DEGs mainly participated in the process of cell adhesion, cell proliferation, survival, invasion, metastasis and angiogenesis. Aberrant expression of PTK2, MAPK signaling pathway, PI3K-Akt signaling pathway, p53 signaling pathway and MET were closely associated with EC carcinogenesis. Importantly, Interleukin 8 (IL8) and C-X-C chemokine receptor type 7 (CXCR-7) were predicted to be significantly related to EC. These findings were further validated by analyzing both TCGA database and our clinical samples of EC. Our discovery provides a registry of genes and pathways that are disrupted in EC, which has the potential to be used in clinic for diagnosis and target therapy of EC in future.
| S-EPMC5739633 | biostudies-literature
Project description:BackgroundThe completion of the sequencing of human, mouse and rat genomes and knowledge of cross-species gene homologies enables studies of differential gene expression in animal models. These types of studies have the potential to greatly enhance our understanding of diseases such as liver cancer in humans. Genes co-expressed across multiple species are most likely to have conserved functions. We have used various bioinformatics approaches to examine microarray expression profiles from liver neoplasms that arise in albumin-SV40 transgenic rats to elucidate genes, chromosome aberrations and pathways that might be associated with human liver cancer.ResultsIn this study, we first identified 2223 differentially expressed genes by comparing gene expression profiles for two control, two adenoma and two carcinoma samples using an F-test. These genes were subsequently mapped to the rat chromosomes using a novel visualization tool, the Chromosome Plot. Using the same plot, we further mapped the significant genes to orthologous chromosomal locations in human and mouse. Many genes expressed in rat 1q that are amplified in rat liver cancer map to the human chromosomes 10, 11 and 19 and to the mouse chromosomes 7, 17 and 19, which have been implicated in studies of human and mouse liver cancer. Using Comparative Genomics Microarray Analysis (CGMA), we identified regions of potential aberrations in human. Lastly, a pathway analysis was conducted to predict altered human pathways based on statistical analysis and extrapolation from the rat data. All of the identified pathways have been known to be important in the etiology of human liver cancer, including cell cycle control, cell growth and differentiation, apoptosis, transcriptional regulation, and protein metabolism.ConclusionThe study demonstrates that the hepatic gene expression profiles from the albumin-SV40 transgenic rat model revealed genes, pathways and chromosome alterations consistent with experimental and clinical research in human liver cancer. The bioinformatics tools presented in this paper are essential for cross species extrapolation and mapping of microarray data, its analysis and interpretation.
| S-EPMC1637037 | biostudies-literature
Project description:BACKGROUND:Bone metastases are common in advanced breast cancer patients and frequently leading to skeletal-related morbidity and deterioration in the quality of life. Although chemotherapy and hormone therapy are able to control the symptoms caused by bone destruction, the underlying molecular mechanisms for the affinity of breast cancer cells towards skeletal bones are still not completely understood. METHODS:In this study, bioinformatic analysis was performed on patients' microarray gene expression data to explore the molecular mechanism associated with breast cancer bone metastasis. Microarray gene expression profile regarding patients with breast cancer and disseminated tumor cells was downloaded from Gene Expression Omnibus (GEO) database (NCBI, NIH). Raw data were normalized and differently expressed genes were identified by using Significance Analysis of Microarrays (SAM) methods. Protein interaction networks were expanded using String. Moreover, molecular functions, biological processes and signaling pathway enrichment analysis were performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). RESULTS:We identified 66 differentially expressed genes. After submitting the set of genes to String, genetic interaction network was expanded, which consisted of 110 nodes and 869 edges. Pathway enrichment analysis suggested that adhesion kinase, ECM-receptor interaction, calcium signaling, Wnt pathways, and PI3K/AKT signaling pathway are highly associated with breast cancer bone metastasis. CONCLUSION:In this study, we established a microarray genetic interaction network associated with breast cancer bone metastasis. This information provides some potential molecular therapeutic targets for breast cancer initiation and progression.
| S-EPMC6156059 | biostudies-literature
Project description:The primary goal of this study is to identify molecular subtypes of breast cancer through gene expression profiles of 327 breast cancer samples and determine molecular and clinical characteristics of different breast cancer subtypes. We studied expression signatures of different cellular functions (e.g., cell proliferation/cell cycle, wound response, tumor stromal response, vascular endothelial normalization, drug esponse genes, etc.) in different breast cancer molecular subtypes and investigated how microarray-based breast cancer molecular subtypes may be used to guide treatment. Gene expression profiles of 327 breast cancer samples were determined using total RNA and Affymetrix U133 plus 2.0 arrays.
| S-ECPF-GEOD-20685 | biostudies-other
Project description:We established cell models of hypoxia, and the number of autophagic vacuoles was observed by electron microscopy. Autophagy associated proteins and invasion were evaluated. RNA sequencing was used to identify DEmRNAs and DEmiRNAs to study the mechanism of hypoxia-induced autophagy in liver cancer cells. Results: We found that hypoxia might promote liver cancer cell invasion by inducing autophagy. In addition, a total of 407 shared DEmRNAs and 57 shared DEmiRNAs were identified in both HCCLM3 autophagy group and SMMC-7721 autophagy group compared with normal controls. Furthermore, 278 DEmRNAs were identified cancer autophagy-specific DEmRNAs and 24 DEmiRNAs were identified cancer autophagy-specific DEmRNA and DEmiRNAs. Finally, we obtained 19 DEmiRNAs with high degree based on the DEmiRNA-DEmRNA interaction network. Among them, hsa-miR-483-5p, hsa-miR-4739, has-miR-214-3p and has-miR-296-5p may be potential gene signatures related to liver cancer autophagy.
2022-05-25 | GSE185853 | GEO
Project description:We established cell models of hypoxia, and the number of autophagic vacuoles was observed by electron microscopy. Autophagy associated proteins and invasion were evaluated. RNA sequencing was used to identify DEmRNAs and DEmiRNAs to study the mechanism of hypoxia-induced autophagy in liver cancer cells. Results: We found that hypoxia might promote liver cancer cell invasion by inducing autophagy. In addition, a total of 407 shared DEmRNAs and 57 shared DEmiRNAs were identified in both HCCLM3 autophagy group and SMMC-7721 autophagy group compared with normal controls. Furthermore, 278 DEmRNAs were identified cancer autophagy-specific DEmRNAs and 24 DEmiRNAs were identified cancer autophagy-specific DEmRNA and DEmiRNAs. Finally, we obtained 19 DEmiRNAs with high degree based on the DEmiRNA-DEmRNA interaction network. Among them, hsa-miR-483-5p, hsa-miR-4739, has-miR-214-3p and has-miR-296-5p may be potential gene signatures related to liver cancer autophagy.
2022-05-25 | GSE185969 | GEO
Project description:The present study identified differentially?expressed genes (DEGs) between pancreatic cancer (PC) tissues and normal tissues, and assessed genetic factors associated with the pathogenesis of PC. The mRNA expression microarray dataset, GSE16515, containing 52 samples, including 16 paired tumor and normal tissue samples, and 20 tumor samples, was downloaded from Gene Expression Omnibus. Raw data were normalized and DEGs were identified. Subsequently, clustering was performed, protein?protein interaction networks were drawn, and functional and pathway enrichment analyses of the DEGs were performed. Copy number variations of DEGs were also identified. A total of 1,765 DEGs between PC and normal tissues were identified, including 1,312 upregulated and 453 downregulated DEGs. Upregulated DEGs were associated with the regulation of nucleocytoplasmic and intracellular transport, whereas downregulated DEGs were associated with the response to organic substances and hormone stimulus. The pancreatic cancer pathway was connected to three DEGs, namely transforming growth factor ?1 (TGFB1), TGF? receptor 1 (TGFBR1) and epidermal growth factor (EGF), which had 2, 3 and 5 CNVs, respectively. These results indicated the important roles of TGFB1, TGFBR1 and EGF in the pathogenesis of PC. These genes may be potential therapeutic targets for the treatment of PC.
| S-EPMC4838162 | biostudies-literature
Project description:Breast cancer (BC) has a complex etiology and pathogenesis, and is the most common malignant tumor type in females, in USA in 2018, yet its relevant molecular mechanisms remain largely unknown. The collagen type V α‑1 chain (COL5A1) gene is differentially expressed in renal and ovarian cancer. Using bioinformatics methods, COL5A1 was determined to also be a significant gene in BC, but its association with BC has not been sufficiently reported. COL5A1 microarray and relevant clinical data were collected from the Gene Expression Omnibus, The Cancer Genome Atlas and other databases to summarize COL5A1 expression in BC and its subtypes at the mRNA and protein levels. All associated information was comprehensively analyzed by various software. The clinical significance of the mutation was obtained via the cBioPortal. Furthermore, Gene Ontology functional annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were also performed to investigate the mechanism of COL5A1 in BC. Immunohistochemistry was also conducted to detect and confirm COL5A1 expression. It was determined that COL5A1 was highly expressed in BC tissues, compared with normal tissues at the mRNA level [standard mean difference, 0.84; 95% confidence interval (CI), 0.60‑1.07; P=0.108]. The area under the summary receiver operator characteristic curve for COL5A1 was 0.87 (95% CI, 0.84‑0.90). COL5A1 expression was altered in 32/817 (4%) sequenced samples. KEGG analysis confirmed the most notable pathways, including focal adhesion, extracellular matrix‑receptor interaction and regulation of the actin cytoskeleton. Immunohistochemical detection was used to verify the expression of COL5A1 in 136 selected cases of invasive BC tissues and 55 cases of adjacent normal tissues, while the rate of high expression of COL5A1 in BC was up to 90.4%. These results indicated that COL5A1 is highly expressed at the mRNA and protein levels in BC, and the prognosis of patients with BC with high COL5A1 expression may be reduced; therefore, COL5A1 may be used independently or combined with other detection factors in BC diagnosis.
| S-EPMC6549075 | biostudies-literature
Project description:Liver ischemia and reperfusion (I/R) injury is of primary concern in cases of liver disease worldwide and is associated with hemorrhagic shock, resection and transplantation. Numerous studies have previously been conducted to investigate the underlying mechanisms of liver I/R injury, however these have not yet been fully elucidated. To determine the difference between ischemia and reperfusion in signaling pathways and the relative pathological mechanisms, the present study downloaded microarray data GSE10657 from the Gene Expression Omnibus database. A total of two data groups from 1?year?old mice were selected for further analysis: i) A total of 90 min ischemia; ii) 90 min ischemia followed by 1 h of reperfusion, n=3 for each group. The Limma package was first used to identify the differentially expressed genes (DEGs). DEGs were subsequently uploaded to the Database for Annotation Visualization and Integrated Discovery online tool for Functional enrichment analysis. A protein?protein interaction (PPI) network was then constructed via STRING version 10.0 and analyzed using Cytoscape software. A total of 114 DEGs were identified, including 21 down and 93 upregulated genes. These DEGs were primarily enriched in malaria and influenza A, in addition to the tumor necrosis factor and mitogen activated protein kinase signaling pathways. Hub genes identified in the PPI network were C?X?C motif chemokine ligand (CXCL) 1, C?C motif chemokine ligand (CCL) 2, interleukin 6, Jun proto?oncogene, activator protein (AP)?1 transcription factor subunit, FOS proto?oncogene, AP?1 transcription factor subunit and dual specificity phosphatase 1. CXCL1 and CCL2 may exhibit important roles in liver I/R injury, with involvement in the immune and inflammatory responses and the chemokine?mediated signaling pathway, particularly at the reperfusion stage. However, further experiments to elucidate the specific roles of these mediators are required in the future.
| S-EPMC5548003 | biostudies-literature