A Comprehensive Data Analysis of Differentially Regulated Genes in Melanoma

2020 ◽  
Author(s):  
Yanjie Han ◽  
Xinxin Li ◽  
Jiliang Yan ◽  
Chunyan Ma ◽  
Xin Wang ◽  
...  

Abstract Background: Melanoma is the most deadly tumor in skin tumors and is prone to distant metastases. The incidence of melanoma has increased rapidly in the past few decades, and current trends indicate that this growth is continuing. This study was aimed to explore the molecular mechanisms of melanoma pathogenesis and discover underlying pathways and genes associated with melanoma.Methods: We used high-throughput expression data to study differential expression profiles of related genes in melanoma. The differentially expressed genes (DEGs) of melanoma in GSE15605, GSE46517, GSE7553 and the Cancer Genome Atlas (TCGA) datasets were analyzed. Differentially expressed genes (DEGs) were identified by paired t-test. Then the DEGs were performed cluster and principal component analyses and protein–protein interaction (PPI) network construction. After that, we analyzed the differential genes through bioinformatics and got hub genes. Finally, the expression of hub genes was confirmed in the TCGA databases and collected patient tissue samples.Results: Total 144 up-regulated DEGs and 16 down-regulated DEGs were identified. A total of 17 gene ontology analysis (GO) terms and 11 pathways were closely related to melanoma. Pathway of pathways in cancer was enriched in 8 DEGs, such as junction plakoglobin (JUP) and epidermal growth factor receptor (EGFR). In the PPI networks, 9 hub genes were obtained, such as loricrin (LOR), filaggrin (FLG), keratin 5 (KRT5), corneodesmosin (CDSN), desmoglein 1 (DSG1), desmoglein 3 (DSG3), keratin 1 (KRT1), involucrin (IVL) and EGFR. The pathway of pathways in cancer and its enriched DEGs may play important roles in the process of melanoma. The hub genes of DEGs may become promising melanoma candidate genes. Five key genes FLG, DSG1, DSG3, IVL and EGFR were identified in the TCGA database and melanoma tissues.Conclusions: The results suggested that FLG, DSG1, DSG3, IVL and EGFR might play important roles and potentially be valuable in the prognosis and treatment of melanoma.

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Cheng Zhang ◽  
Bingye Zhang ◽  
Di Meng ◽  
Chunlin Ge

Abstract Background The incidence of cholangiocarcinoma (CCA) has risen in recent years, and it has become a significant health burden worldwide. However, the mechanisms underlying tumorigenesis and progression of this disease remain largely unknown. An increasing number of studies have demonstrated crucial biological functions of epigenetic modifications, especially DNA methylation, in CCA. The present study aimed to identify and analyze methylation-regulated differentially expressed genes (MeDEGs) involved in CCA tumorigenesis and progression by bioinformatics analysis. Methods The gene expression profiling dataset (GSE119336) and gene methylation profiling dataset (GSE38860) were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) were identified using the limma packages of R and GEO2R, respectively. The MeDEGs were obtained by overlapping the DEGs and DMGs. Functional enrichment analyses of these genes were then carried out. Protein–protein interaction (PPI) networks were constructed using STRING and visualized in Cytoscape to determine hub genes. Finally, the results were verified based on The Cancer Genome Atlas (TCGA) database. Results We identified 98 hypermethylated, downregulated genes and 93 hypomethylated, upregulated genes after overlapping the DEGs and DMGs. These genes were mainly enriched in the biological processes of the cell cycle, nuclear division, xenobiotic metabolism, drug catabolism, and negative regulation of proteolysis. The top nine hub genes of the PPI network were F2, AHSG, RRM2, AURKB, CCNA2, TOP2A, BIRC5, PLK1, and ASPM. Moreover, the expression and methylation status of the hub genes were significantly altered in TCGA. Conclusions Our study identified novel methylation-regulated differentially expressed genes (MeDEGs) and explored their related pathways and functions in CCA, which may provide novel insights into a further understanding of methylation-mediated regulatory mechanisms in CCA.


2021 ◽  
Author(s):  
Han Wang ◽  
Jieqing Chen ◽  
Xinhui Liao ◽  
Yang Liu ◽  
Aifa Tang ◽  
...  

Abstract BACKGROUND and OBJECTIVE: A better understanding of the molecular mechanisms underlying bladder cancer is necessary to identify candidate therapeutic targets. METHODS: We screened for genes associated with bladder cancer progression and prognosis. Publicly available expression data were obtained from TCGA and GEO to identify differentially expressed genes (DEGs) between bladder cancer and normal bladder tissues. Weighted co-expression networks were constructed, and Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Associations between hub genes and immune infiltration and immune therapy were evaluated. RESULTS: 3461 DEGs in TCGA-BC and 1069 DEGs in the GSE dataset were identified, with 87 overlapping differentially expressed genes between the bladder cancer and normal bladder groups. Hub genes in the tumour group were mainly enriched for cell proliferation-related GO terms and KEGG pathways, while hub genes in the normal group were related to the synthesis and secretion of neurotransmitters. PPI networks for the genes identified in the normal and tumour groups were constructed. Based on a survival analysis, CDH19, RELN, PLP1, and TRIB3 were significantly associated with prognosis (P < 0.05). Four hub genes were significantly enriched in the MAPK signalling pathway, VEGF signalling pathway, WNT signalling pathway, cell cycle, and P53 signalling pathway based on a gene set enrichment analysis; these genes were associated with immune infiltration levels in bladder cancer. CONCLUSIONS: CDH19, RELN, PLP1, and TRIB3 may play important roles in the development of bladder cancer and are potential therapeutic and prognostic targets.


PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7135 ◽  
Author(s):  
Fangcao Lei ◽  
Han Zhang ◽  
Xiaoli Xie

Background Pulpitis is a common inflammatory disease that affects dental pulp. It is important to understand the molecular signals of inflammation and repair associated with this process. Increasing evidence has revealed that long noncoding RNAs (lncRNAs), via competitively sponging microRNAs (miRNAs), can act as competing endogenous RNAs (ceRNAs) to regulate inflammation and reparative responses. The aim of this study was to elucidate the potential roles of lncRNA, miRNA and messenger RNA (mRNA) ceRNA networks in pulpitis tissues compared to normal control tissues. Methods The oligo and limma packages were used to identify differentially expressed lncRNAs and mRNAs (DElncRNAs and DEmRNAs, respectively) based on expression profiles in two datasets, GSE92681 and GSE77459, from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were further analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Protein–protein interaction (PPI) networks and modules were established to screen hub genes using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and the Molecular Complex Detection (MCODE) plugin for Cytoscape, respectively. Furthermore, an lncRNA-miRNA-mRNA-hub genes regulatory network was constructed to investigate mechanisms related to the progression and prognosis of pulpitis. Then, quantitative real-time polymerase chain reaction (qRT-PCR) was applied to verify critical lncRNAs that may significantly affect the pathogenesis in inflamed and normal human dental pulp. Results A total of 644 upregulated and 264 downregulated differentially expressed genes (DEGs) in pulpitis samples were identified from the GSE77459 dataset, while 8 up- and 19 downregulated probes associated with lncRNA were identified from the GSE92681 dataset. Protein–protein interaction (PPI) based on STRING analysis revealed a network of DEGs containing 4,929 edges and 623 nodes. Upon combined analysis of the constructed PPI network and the MCODE results, 10 hub genes, including IL6, IL8, PTPRC, IL1B, TLR2, ITGAM, CCL2, PIK3CG, ICAM1, and PIK3CD, were detected in the network. Next, a ceRNA regulatory relationship consisting of one lncRNA (PVT1), one miRNA (hsa-miR-455-5p) and two mRNAs (SOCS3 and PLXNC1) was established. Then, we constructed the network in which the regulatory relationship between ceRNA and hub genes was summarized. Finally, our qRT-PCR results confirmed significantly higher levels of PVT1 transcript in inflamed pulp than in normal pulp tissues (p = 0.03). Conclusion Our study identified a novel lncRNA-mediated ceRNA regulatory mechanisms in the pathogenesis of pulpitis.


2021 ◽  
Author(s):  
Yuan-Mei Lou ◽  
Yan-Zhi Ge ◽  
Wen Chen ◽  
Lin Su ◽  
Jia-Qi Zhang ◽  
...  

Abstract Purpose: Irritable bowel syndrome with diarrhea (IBS-D) is a common functional gastrointestinal disorder around the world. However, the molecular mechanisms of IBS-D are still not well understood. This study was designed to identify key biomarkers and immune infiltration in the rectal mucosa of IBS-D by bioinformatics analysis. Methods: The gene expression profiles of GSE36701 were downloaded from the GEO database. The differentially expressed genes (DEGs) were identified and functional enrichment and pathway analyses were performed. Using STRING and Cytoscape, protein-protein interaction (PPI) networks were constructed and core genes were identified. Subsequently, 22 immune cell types of IBS-D tissues were explored by the Cell type Identification by Estimating Relative Subsets of RNA Transcripts. Finally, the co-expression network of DEGs was estimated by the weigh gene co-expression network analysis method to identify IBS-D-related modules and deeply hub genes. Results: 224 up-regulated and 171 down-regulated genes in IBS-D patients: Our analysis indicated that several DEGs might play crucial roles in IBS-D, such as CDC20, UBE2C, AURKA, CDC26, CKS1B and PSMB3. Later, we found that immune infiltrating cells such as T cells CD4 memory resting, M2 macrophages are crucial in IBS-D progression. In the end, a total of 9 co-expression gene modules were calculated and the black module was found to have the highest correlation. 15 hub genes were identified both in DEGs and the black module. Conclusions: This study identified molecular mechanisms and a series of candidate genes as well as significant pathways from the bioinformatics network, which may provide a diagnostic method and therapeutic targets for IBS-D.


Hereditas ◽  
2021 ◽  
Vol 158 (1) ◽  
Author(s):  
Haoming Li ◽  
Linqing Zou ◽  
Jinhong Shi ◽  
Xiao Han

Abstract Background Alzheimer’s disease (AD) is a fatal neurodegenerative disorder, and the lesions originate in the entorhinal cortex (EC) and hippocampus (HIP) at the early stage of AD progression. Gaining insight into the molecular mechanisms underlying AD is critical for the diagnosis and treatment of this disorder. Recent discoveries have uncovered the essential roles of microRNAs (miRNAs) in aging and have identified the potential of miRNAs serving as biomarkers in AD diagnosis. Methods We sought to apply bioinformatics tools to investigate microarray profiles and characterize differentially expressed genes (DEGs) in both EC and HIP and identify specific candidate genes and pathways that might be implicated in AD for further analysis. Furthermore, we considered that DEGs might be dysregulated by miRNAs. Therefore, we investigated patients with AD and healthy controls by studying the gene profiling of their brain and blood samples to identify AD-related DEGs, differentially expressed miRNAs (DEmiRNAs), along with gene ontology (GO) analysis, KEGG pathway analysis, and construction of an AD-specific miRNA–mRNA interaction network. Results Our analysis identified 10 key hub genes in the EC and HIP of patients with AD, and these hub genes were focused on energy metabolism, suggesting that metabolic dyshomeostasis contributed to the progression of the early AD pathology. Moreover, after the construction of an miRNA–mRNA network, we identified 9 blood-related DEmiRNAs, which regulated 10 target genes in the KEGG pathway. Conclusions Our findings indicated these DEmiRNAs having the potential to act as diagnostic biomarkers at an early stage of AD.


2021 ◽  
Author(s):  
Feifei Liu ◽  
Yu Wang ◽  
Wenxue Li ◽  
Diancheng Li ◽  
Yuwei Xin ◽  
...  

Abstract Background: Colorectal cancer (CRC) is one of the most common malignancies of the digestive system; the progression and prognosis of which are affected by a complicated network of genes and pathways. The aim of this study was to identify potential hub genes associated with the progression and prognosis of colorectal cancer (CRC).Methods: We obtained gene expression profiles from GEO database to search differentially expressed genes (DEGs) between CRC tissues and normal tissue. Subsequently, we conducted a functional enrichment analysis, generated a protein–protein interaction (PPI) network to identify the hub genes, and analyzed the expression validation of the hub genes. Kaplan–Meier plotter survival analysis tool was performed to evaluate the prognostic value of hub genes expression in CRC patients.Results: A total of 370 samples, involving CRC and normal tissues were enrolled in this article. 283 differentially expressed genes (DEGs), including 62 upregulated genes and 221 downregulated genes between CRC and normal tissues were selected. We finally filtered out 6 hub genes, including INSL5, MTIM, GCG, SPP1, HSD11B2, and MAOB. In the database of TCGA-COAD, the mRNA expression of INSL5, MT1M, HSD11B2, MAOB in tumor is lower than that in normal; the mRNA expression of SPP1 in tumor is higher than that in normal. In the HPA database, the expression of INSL5, GCG, HSD11B2, MAOB in tumor is lower than that in normal tissues; the expression of SPP1 in the tumor is higher than that in normal tissues. Survival analysis revealed that INSL5, GCG, SPP1 and MT1M may serve as prognostic biomarkers in CRC. Conclusions: We screened out six hub genes to predict the occurrence and prognosis of patients with CRC using bioinformatics methods, which may provide new targets and ideas for diagnosis, prognosis and individualized treatment for CRC.


2021 ◽  
Author(s):  
Li Guoquan ◽  
Du Junwei ◽  
He Qi ◽  
Fu Xinghao ◽  
Ji Feihong ◽  
...  

Abstract BackgroundHashimoto's thyroiditis (HT), also known as chronic lymphocytic thyroiditis, is a common autoimmune disease, which mainly occurs in women. The early manifestation was hyperthyroidism, however, hypothyroidism may occur if HT was not controlled for a long time. Numerous studies have shown that multiple factors, including genetic, environmental, and autoimmune factors, were involved in the pathogenesis of the disease, but the exact mechanisms were not yet clear. The aim of this study was to identify differentially expressed genes (DEGs) by comprehensive analysis and to provide specific insights into HT. MethodsTwo gene expression profiles (GSE6339, GSE138198) about HT were downloaded from the Gene Expression Omnibus (GEO) database. The DEGs were assessed between the HT and normal groups using the GEO2R. The DEGs were then sent to the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The hub genes were discovered using Cytoscape and CytoHubba. Finally, NetworkAnalyst was utilized to create the hub genes' targeted microRNAs (miRNAs). ResultsA total of 62 DEGs were discovered, including 60 up-regulated and 2 down-regulated DEGs. The signaling pathways were mainly engaged in cytokine interaction and cytotoxicity, and the DEGs were mostly enriched in immunological and inflammatory responses. IL2RA, CXCL9, IL10RA, CCL3, CCL4, CCL2, STAT1, CD4, CSF1R, and ITGAX were chosen as hub genes based on the results of the protein-protein interaction (PPI) network and CytoHubba. Five miRNAs, including mir-24-3p, mir-223-3p, mir-155-5p, mir-34a-5p, mir-26b-5p, and mir-6499-3p, were suggested as likely important miRNAs in HT. ConclusionsThese hub genes, pathways and miRNAs contribute to a better understanding of the pathophysiology of HT and offer potential treatment options for HT.


2020 ◽  
Author(s):  
Na Li ◽  
Ru-feng Bai ◽  
Chun Li ◽  
Li-hong Dang ◽  
Qiu-xiang Du ◽  
...  

Abstract Background: Muscle trauma frequently occurs in daily life. However, the molecular mechanisms of muscle healing, which partly depend on the extent of the damage, are not well understood. This study aimed to investigate gene expression profiles following mild and severe muscle contusion, and to provide more information about the molecular mechanisms underlying the repair process.Methods: A total of 33 rats were divided randomly into control (n = 3), mild contusion (n = 15), and severe contusion (n = 15) groups; the contusion groups were further divided into five subgroups (1, 3, 24, 48, and 168 h post-injury; n = 3 per subgroup). Then full genome microarray of RNA isolated from muscle tissue was performed to access the gene expression changes during healing process.Results: A total of 2,844 and 2,298 differentially expressed genes were identified in the mild and severe contusion groups, respectively. The analysis of the overlapping differentially expressed genes showed that there are common mechanisms of transcriptomic repair of mild and severe contusion within 48 h post-contusion. This was supported by the results of principal component analysis, hierarchical clustering, and weighted gene co‐expression network analysis of the 1,620 coexpressed genes in mildly and severely contused muscle. From these analyses, we discovered that the gene profiles in functional modules and temporal clusters were similar between the mild and severe contusion groups; moreover, the genes showed time-dependent patterns of expression, which allowed us to identify useful markers of wound age. We then performed an analysis of the functions of genes (including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway annotation, and protein–protein interaction network analysis) in the functional modules and temporal clusters, and the hub genes in each module–cluster pair were identified. Interestingly, we found that genes downregulated within 24−48 h of the healing process were largely associated with metabolic processes, especially oxidative phosphorylation of reduced nicotinamide adenine dinucleotide phosphate, which has been rarely reported. Conclusions: These results improve our understanding of the molecular mechanisms underlying muscle repair, and provide a basis for further studies of wound age estimation.


2021 ◽  
Author(s):  
Ke-Ying Fang ◽  
Gui-Ning Liang ◽  
Zhuo-Qing Zhuang ◽  
Yong-Xin Fang ◽  
Yu-Qian Dong ◽  
...  

Abstract Background: With the worldwide spread of COVID-19, people’s health and social order have been exposed to enormous risks. After encountering patients who test positive again after discharge, our study analyzed the pathogenesis to further assess the risk and possibility of virus reactivation.Methods: A separate microarray was acquired from the Integrated Gene Expression System (GEO), and its samples were divided into two groups: a “convalescent-RTP” group consisting of recovery and “retesting-positive” (RTP) patients (group CR) and a “health-RTP” group consisting of healthy control and RTP patients (group HR). The enrichment analysis was performed with R software, obtaining the gene ontology (GO) and Kyoto pluripotent stem cells (KEGG) of the genes and genomes. Subsequently, the protein–protein interaction (PPI) networks of each group were established and the hub genes were discovered using the cytoHubba plug-in.Results: In this study, 20 differentially expressed genes were identified, and 6622 genes were identified in the group CR, consisting of 5003 up-regulated and 1619 down-regulated genes. Meanwhile, 7335 genes were screened in the group HR, including 4323 up-regulated and 3012 down-regulated ones. The GO and KEGG analysis of the two groups revealed significant enrichment of these differentially expressed genes in pathways associated with immune response and apoptosis. In the PPI network constructed, 10 hub genes in group CR were identified, including TP53BP1, SNRPD1, SNRPD2, SF3B1, SNRNP200, MRPS16, MRPS9, CALM1, PPP2R1A, YWHAZ. Similarly, TP53BP1, RPS15, EFTUD2, MRPL16, MRPL17, MRPS14, RPL35A, MRPL32, MRPS6, POLR2G were selected as hub genes.Conclusions: Using the messenger ribonucleic acid (mRNA) expression data from GSE166253, we explore the pathogenesis of retesting positive in COVID-19 from the immune mechanism and molecular level. We found TP53BP1, SNRPD1 and SNRPD2 as hub genes in RTP patients. Hence, their regulatory pathway is vital to the management and prognostic prediction of RTP patients, rendering the further study of these hub genes necessary.


2013 ◽  
Vol 40 (12) ◽  
pp. 1249 ◽  
Author(s):  
Hai-fen Li ◽  
Xiao-Ping Chen ◽  
Fang-he Zhu ◽  
Hai-Yan Liu ◽  
Yan-Bin Hong ◽  
...  

Peanut (Arachis hypogaea L.) produces flowers aerially, but the fruit develops underground. This process is mediated by the gynophore, which always grows vertically downwards. The genetic basis underlying gravitropic bending of gynophores is not well understood. To identify genes related to gynophore gravitropism, gene expression profiles of gynophores cultured in vitro with tip pointing upward (gravitropic stimulation sample) and downward (control) at both 6 and 12 h were compared through a high-density peanut microarray. After gravitropic stimulation, there were 174 differentially expressed genes, including 91 upregulated and 83 downregulated genes at 6 h, and 491 differentially expressed genes including 129 upregulated and 362 downregulated genes at 12 h. The differentially expressed genes identified were assigned to 24 functional categories. Twenty pathways including carbon fixation, aminoacyl-tRNA biosynthesis, pentose phosphate pathway, starch and sucrose metabolism were identified. The quantitative real-time PCR analysis was performed for validation of microarray results. Our study paves the way to better understand the molecular mechanisms underlying the peanut gynophore gravitropism.


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