Identification of Hub Genes Associated with Melanoma Development by Comprehensive Bioinformatics Analysis

Abstract Introduction: The aim of this study was to identify important genes associated with melanoma for further development of new target gene therapies and to analyze their significance in relation to prognosis.Materials and methods: Gene expression data for melanoma and normal tissue were downloaded from three databases. Differentially co-expressed genes were identified by WGCNA and DEGs analysis. These genes were subjected to GO and KEGG enrichment analysis as well as construction of the PPI, visualized with Cytoscape, and screened for the top 10 Hub genes using CytoHubba. We verified the protein levels of the Hub gene using the HPA database.Results: A total of 435 differentially co-expressed genes were obtained. Survival curves showed that high expression of FOXM1, EXO1, KIF20A, TPX2 and CDC20 in melanoma patients with 5 of the top 10 hub genes was associated with reduced overall survival (OS). The HPA database results showed that FOXM1, KIF20A, TPX2 and CDC20 showed upregulated expression in melanoma compared to normal tissues.Conclusion: FOXM1, KIF20A, TPX2, and CDC20 are prognosis-associated core genes of melanoma, and their high expression correlates with low prognosis of melanoma patients, and can be used as biomarkers for melanoma diagnosis, treatment, and prognosis prediction.

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Identification of Hub Genes Associated With Melanoma Development by Comprehensive Bioinformatics Analysis

Frontiers in Oncology ◽

10.3389/fonc.2021.621430 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jie Jiang ◽

Chong Liu ◽

Guoyong Xu ◽

Tuo Liang ◽

Chaojie Yu ◽

...

Keyword(s):

Target Gene ◽

Enrichment Analysis ◽

High Expression ◽

Expression Data ◽

Hub Genes ◽

Gene Therapies ◽

Protein Levels ◽

Melanoma Diagnosis ◽

Melanoma Patients ◽

Core Genes

IntroductionThis study aimed to identify important genes associated with melanoma to further develop new target gene therapies and analyze their significance concerning prognosis.Materials and methodsGene expression data for melanoma and normal tissue were downloaded from three databases. Differentially co-expressed genes were identified by WGCNA and DEGs analysis. These genes were subjected to GO, and KEGG enrichment analysis and construction of the PPI visualized with Cytoscape and screened for the top 10 Hub genes using CytoHubba. We validated the Hub gene’s protein levels with an immunohistochemical assay to confirm the accuracy of our analysis.ResultsA total of 435 differentially co-expressed genes were obtained. Survival curves showed that high expression of FOXM1,\ EXO1, KIF20A, TPX2, and CDC20 in melanoma patients with 5 of the top 10 hub genes was associated with reduced overall survival (OS). Immunohistochemistry showed that all five genes were expressed at higher protein levels in melanoma than in paracancerous tissues.ConclusionFOXM1, EXO1, KIF20A, TPX2, and CDC20 are prognosis-associated core genes of melanoma, and their high expression correlates with the low prognosis of melanoma patients and can be used as biomarkers for melanoma diagnosis, treatment, and prognosis prediction.

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Identification of Hub Genes Associated with Melanoma Development by Comprehensive Bioinformatics Analysis

10.21203/rs.3.rs-101310/v1 ◽

2020 ◽

Author(s):

Jie Jiang ◽

Guoyong Xu ◽

Tuo Liang ◽

Chaojie Yu ◽

Shian Liao ◽

...

Keyword(s):

Target Gene ◽

Enrichment Analysis ◽

High Expression ◽

Expression Data ◽

Hub Genes ◽

Gene Therapies ◽

Protein Levels ◽

Melanoma Diagnosis ◽

Melanoma Patients ◽

Core Genes

Abstract Introduction: This study aimed to identify important genes associated with melanoma to further develop new target gene therapies and analyze their significance concerning prognosis.Materials and methods: Gene expression data for melanoma and normal tissue were downloaded from three databases. Differentially co-expressed genes were identified by WGCNA and DEGs analysis. These genes were subjected to GO, and KEGG enrichment analysis and construction of the PPI visualized with Cytoscape and screened for the top 10 Hub genes using CytoHubba. We validated the Hub gene's protein levels with an immunohistochemical assay to confirm the accuracy of our analysis.Results: A total of 435 differentially co-expressed genes were obtained. Survival curves showed that high expression of FOXM1, EXO1, KIF20A, TPX2, and CDC20 in melanoma patients with 5 of the top 10 hub genes was associated with reduced overall survival (OS). Immunohistochemistry showed that all five genes were expressed at higher protein levels in melanoma than in paracancerous tissues.Conclusion: FOXM1, EXO1, KIF20A, TPX2, and CDC20 are prognosis-associated core genes of melanoma, and their high expression correlates with the low prognosis of melanoma patients and can be used as biomarkers for melanoma diagnosis, treatment, and prognosis prediction.

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Identification of Prognostic Biomarkers of Potential Hub Genes in Urothelial Carcinoma and Function in Microenvironment

10.21203/rs.3.rs-502631/v1 ◽

2021 ◽

Author(s):

Wei Chu ◽

Bing Zhang ◽

Haifeng Gong ◽

Qianqian Zhao ◽

Jun Chen ◽

...

Keyword(s):

T Cells ◽

Urothelial Carcinoma ◽

Checkpoint Inhibitors ◽

Expression Profiles ◽

Enrichment Analysis ◽

Receptor Interaction ◽

Hub Genes ◽

Database Analysis ◽

Protein Levels ◽

Normal Tissues

Abstract Background Urothelial carcinoma (UC) is the most common histological type of urinary system. In the past decades, despite the advances in UC diagnosis and therapy, there are still challenges to improve the overall survival (OS) of UC patients. PD-L1 inhibitor and PD-1 inhibitor have been approved for treating invasive UC, however, only about 20% of patients with metastatic UC show clinical benefits from immune checkpoint inhibitors. Therefor, bioinformatics tools were utilized to screen prognostic-related biomarkers, and analyze their relationship with immunocyte in UC, hoping to provide new ideas for the clinical treatment of UC patients.Methods Three gene expression profiles (i.e. GSE32548, GSE32894 and GSE48075) were selected from GEO, and divide them into invasive and superficial UC group for study. NetworkAnalyst tool was used to construct gene regulatory network of DEGs, while DAVID and Metascape were utilized to perform gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis of DEGs. The hub genes were screened by STRING and cytoscape, and the ONCOMINE, GEPIA, UALCAN, cBioPortal and HPA databases were used to analyze the expression differences and survival curves of UC at the DNA, RNA, protein levels and protein levels. TIMER was used to analyze the relationship between hub genes and immunocyte infiltration.Results In total, 63 DEGs were identified from the GEO database of UC, of which 31 and 32 were up-and down-regulated. GO/KEGG pathway analysis identified DEGs were mainly enriched in the collagen catabolic process, extracellular matrix (ECM) organization, ECM structural constituent and ECM-receptor interaction. Nine hub genes (i.e. COL1A1, COL1A2, COL3A1, COL5A2, MMP9, POSTN, SPP1, VCAN and THBS2) upregulated in invasive UC compared with superficial UC were identified. cBioportal database analysis showed that 35% of UC patients presented genetic variants in the hub genes, of which amplification and deletion mutations were the most common. ONCOMINE and UALCAN database analysis showed that the mRNA expression of all hub genes in invasive UC was significantly higher than that in superficial UC and normal tissues. HPA database analysis showed that there was up-regulation of COL3A1, SPP1, POSTN and VCAN protein in UC tissues than in normal tissues. GEPIA showed that COL1A2, COL3A1, THBS2, and VCAN were positively correlated with the OS rate among patients with UC (P < 0.05). UALCAN showed that UC patients with high expression of COL1A1, COL1A2, COL5A2 and POSTN had a poorer prognosis (P < 0.05). TRRUST database analysis indicated that there was a significant correlation between the expression of the hub genes and the infiltration of CD4 + T cells, CD8 + T cells, macrophages, neutrophils and dendritic cells.Conclusion Hub genes played important roles in pathogenesis and treatment prognosis of UC. Hub genes analysis provides new predictive biomolecules for UC immunotherapy and prognosis judgment.

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Screening of cervical cancer-related hub genes based on comprehensive bioinformatics analysis

Cancer Biomarkers ◽

10.3233/cbm-203262 ◽

2021 ◽

pp. 1-13

Author(s):

Simei Tu ◽

Hao Zhang ◽

Xiaocheng Yang ◽

Wen Wen ◽

Kangjing Song ◽

...

Keyword(s):

Gene Expression ◽

Cervical Cancer ◽

Molecular Mechanisms ◽

Disease Free Survival ◽

The Cancer Genome Atlas ◽

Mrna Levels ◽

Hub Genes ◽

Normal Tissues ◽

Significant Difference ◽

Core Genes

BACKGROUND: Since the molecular mechanisms of cervical cancer (CC) have not been completely discovered, it is of great significance to identify the hub genes and pathways of this disease to reveal the molecular mechanisms of cervical cancer. OBJECTIVE: The study aimed to identify the biological functions and prognostic value of hub genes in cervical cancer. METHODS: The gene expression data of CC patients were downloaded from the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database. The core genes were screened out by differential gene expression analysis and weighted gene co-expression network analysis (WGCNA). R software, the STRING online tool and Cytoscape software were used to screen out the hub genes. The GEPIA public database was used to further verify the expression levels of the hub genes in normal tissues and tumour tissues and determine the disease-free survival (DFS) rates of the hub genes. The protein expression of the survival-related hub genes was identified with the Human Protein Atlas (HPA) database. RESULTS: A total of 64 core genes were screened, and 10 genes, including RFC5, POLE3, RAD51, RMI1, PALB2, HDAC1, MCM4, ESR1, FOS and E2F1, were identified as hub genes. Compared with that in normal tissues, RFC5, POLE3, RAD51,RMI1, PALB2, MCM4 and E2F1 were all significantly upregulated in cervical cancer, ESR1 was significantly downregulated in cervical cancer, and high RFC5 expression in CC patients was significantly related to OS. In the DFS analysis, no significant difference was observed in the expression level of RFC5 in cervical cancer patients. Finally, RFC5 protein levels verified by the HPA database were consistently upregulated with mRNA levels in CC samples. CONCLUSIONS: RFC5 may play important roles in the occurrence and prognosis of CC. It could be further explored and validated as a potential predictor and therapeutic target for CC.

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LINC01128 expedites cervical cancer progression by regulating miR-383-5p/SFN axis

BMC Cancer ◽

10.1186/s12885-019-6326-5 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 5

Author(s):

Yi Hu ◽

Yan Ma ◽

Jie Liu ◽

Yanlin Cai ◽

Mengmeng Zhang ◽

...

Keyword(s):

Cervical Cancer ◽

Cell Proliferation ◽

Cancer Progression ◽

Cell Apoptosis ◽

High Expression ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Real Time Quantitative Pcr ◽

Protein Levels ◽

Normal Tissues

Abstract Background Cervical cancer (CC), causing significant morbidity and mortality worldwide, is one of the most common gynecological malignancies in women. SFN has been reported as a potential prognostic marker with apparent high expression in tumors. Nevertheless, the function mechanism of SFN is not clear yet in CC. Methods The relative expressions of RNAs were detected by real-time quantitative PCR (RT-qPCR). Colony formation assay, EdU stained assay and CCK-8 assay were to check cell proliferation ability in CC. Flow cytometry and apoptosis related proteins analysis were used to measure cells apoptosis capacity. Luciferase reporter assay and RNA pull down assay were to verify the molecular mechanism. Results SFN was highly expressed in CC tissues and CC cell lines compared with normal tissues and normal cell line. After interfering SFN, cell proliferation, migration and invasion ability was inhibited as well as cell apoptosis ability was promoted. In subsequence, miR-383-5p exhibited conspicuous low expression in CC tissues. And miR-383-5p was found to bind to SFN and have anti-cancerous effects in CC. Moreover, LINC01128 displayed remarkable high expression in CC tissues. Besides, LINC01128 shortage could reduce the expression of SFN at mRNA and protein levels. And the affinity between LINC01128 and miR-383-5p was verified. In the end, it was proved that LINC01128 could enhance cell proliferation, migration and invasion as well as inhibit cell apoptosis by binding with miR-383-5p and upregulating SFN. Conclusion LINC01128 expedited cells cellular process in CC by binding with miR-383-5p to release SFN. Graphical Abstract

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Integrated WGCNA and PPI Network to Screen Hub Genes Signatures for Infantile Hemangioma

Frontiers in Genetics ◽

10.3389/fgene.2020.614195 ◽

2021 ◽

Vol 11 ◽

Author(s):

Miao Xu ◽

Tianxiang Ouyang ◽

Kaiyang Lv ◽

Xiaorong Ma

Keyword(s):

Differential Expression ◽

Enrichment Analysis ◽

Infantile Hemangioma ◽

Ppi Network ◽

Hub Genes ◽

Protein Protein Interaction ◽

Normal Tissues ◽

Network Analyses ◽

Cycle Arrest ◽

Auc Value

BackgroundInfantile hemangioma (IH) is characterized by proliferation and regression.MethodsBased on the GSE127487 dataset, the differentially expressed genes (DEGs) between 6, 12, or 24 months and normal samples were screened, respectively. STEM software was used to screen the continued up-regulated or down-regulated in common genes. The modules were assessed by weighted gene co-expression network analysis (WGCNA). The enrichment analysis was performed to identified the biological function of important module genes. The area under curve (AUC) value and protein-protein interaction (PPI) network were used to identify hub genes. The differential expression of hub genes in IH and normal tissues was detected by qPCR.ResultsThere were 5,785, 4,712, and 2,149 DEGs between 6, 12, and 24 months and normal tissues. We found 1,218 DEGs were up-regulated or down-regulated expression simultaneously in common genes. They were identified as 10 co-expression modules. Module 3 and module 4 were positively or negatively correlated with the development of IH, respectively. These two module genes were significantly involved in immunity, cell cycle arrest and mTOR signaling pathway. The two module genes with AUC greater than 0.8 at different stages of IH were put into PPI network, and five genes with the highest degree were identified as hub genes. The differential expression of these genes was also verified by qRTPCR.ConclusionFive hub genes may distinguish for proliferative and regressive IH lesions. The WGCNA and PPI network analyses may help to clarify the molecular mechanism of IH at different stages.

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Using Weighted Gene Co-Expression Network Analysis to Identify Key Genes Related to the Onset of Preeclampsia

10.21203/rs.3.rs-87182/v1 ◽

2020 ◽

Author(s):

Xinyang Shen ◽

Zhijian Wang ◽

Zhirui Zeng ◽

Zhenqin Huang ◽

Xiaowei Huang ◽

...

Keyword(s):

Enrichment Analysis ◽

Diagnostic Value ◽

Functional Enrichment ◽

Immune Response Gene ◽

Control Group ◽

Ppi Network ◽

Hub Genes ◽

Ontology Term ◽

Gene Data ◽

Core Genes

Abstract Background: Preeclampsia is a form of hypertension in pregnancy, which induced by complicated factors. However, the pathogenesis of the disease is unclear. The present study was aimed to discover the critical biomarkers associated with the occurrence and development of preeclampsia. Methods：Gene data profile GSE75010 was downloaded from the Gene Expression Omnibus (GEO) database and used as discovery cohort to establish a WGCNA network determining significant modules which associated with clinical traits. Subsequently, functional enrichment analysis, pathway analysis and protein-protein interaction (PPI) network construction were performed on the core genes in significant modules to identify hub genes. Then, gene data profile GSE25906 was used as verified cohort to determine their diagnostic value of hub genes. The protein expression levels of these hub genes in preeclampsia and control placental tissues were verified using immunohistochemistry method. Finally, GSEA was performed to analyze their enrichment pathways. Results: Total 33 co-expression modules were identified after the establishment of WGCNA, of which 4 gene modules were identified as significant modules because they were related to multiple (>3) clinical traits. Total 75 core genes in significant modules were analyzed, and results showed that they were mainly enriched in adaptive immune response (Gene Ontology term) and platelet activation (Kyoto Encyclopedia of Genes and Genomes term). Finally, a total of 5 genes including TYROBP, PLEK, LCP2, HCK, ITGAM were identified as hub genes which scored high in PPI network and had high diagnostic value. Furthermore, the protein level of these 5 genes in placental tissues of preeclampsia was lower than that of the control group. Moreover, these 5 genes were all enriched in 17 pathways, including autoimmunity pathway. Conclusions：These 5 genes (TYROBP, PLEK, LCP2, HCK, ITGAM) may be closely related to the pathogenesis of preeclampsia, which may also help the diagnosis and therapy of preeclampsia.

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Bioinformatics analysis of potential core genes for glioblastoma

Bioscience Reports ◽

10.1042/bsr20201625 ◽

2020 ◽

Vol 40 (7) ◽

Author(s):

Yu Zhang ◽

Xin Yang ◽

Xiao-Lin Zhu ◽

Jia-Qi Hao ◽

Hao Bai ◽

...

Keyword(s):

Survival Analysis ◽

Protein Interactions ◽

Poor Prognosis ◽

Enrichment Analysis ◽

Differentially Expressed ◽

Pathway Enrichment Analysis ◽

Normal Brain ◽

Hub Genes ◽

Potential Core ◽

Core Genes

Abstract Background: Glioblastoma (GBM) has a high degree of malignancy, aggressiveness and recurrence rate. However, there are limited options available for the treatment of GBM, and they often result in poor prognosis and unsatisfactory outcomes. Materials and methods: In order to identify potential core genes in GBM that may provide new therapeutic insights, we analyzed three gene chips (GSE2223, GSE4290 and GSE50161) screened from the GEO database. Differentially expressed genes (DEG) from the tissues of GBM and normal brain were screened using GEO2R. To determine the functional annotation and pathway of DEG, Gene Ontology (GO) and KEGG pathway enrichment analysis were conducted using DAVID database. Protein interactions of DEG were visualized using PPI network on Cytoscape software. Next, 10 Hub nodes were screened from the differentially expressed network using MCC algorithm on CytoHubba software and subsequently identified as Hub genes. Finally, the relationship between Hub genes and the prognosis of GBM patients was described using GEPIA2 survival analysis web tool. Results: A total of 37 up-regulated and 187 down-regulated genes were identified through microarray analysis. Amongst the 10 Hub genes selected, SV2B appeared to be the only gene associated with poor prognosis in glioblastoma based on the survival analysis. Conclusion: Our study suggests that high expression of SV2B is associated with poor prognosis in GBM patients. Whether SV2B can be used as a new therapeutic target for GBM requires further validation.

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Identification of the Crucial Gene in Overflow Arteriovenous Fistula by Bioinformatics Analysis

Frontiers in Physiology ◽

10.3389/fphys.2021.621830 ◽

2021 ◽

Vol 12 ◽

Author(s):

Zhengde Zhao ◽

Qining Fu ◽

Liangzhu Hu ◽

Yangdong Liu

Keyword(s):

Signaling Pathways ◽

Signaling Pathway ◽

Intimal Hyperplasia ◽

Enrichment Analysis ◽

Mapk Signaling ◽

Mapk Signaling Pathway ◽

Biological Processes ◽

Hub Genes ◽

Av Fistula ◽

Core Genes

Objective: The aim was to study the preliminary screening of the crucial genes in intimal hyperplasia in the venous segment of arteriovenous (AV) fistula and the underlying potential molecular mechanisms of intimal hyperplasia with bioinformatics analysis.Methods: The gene expression profile data (GSE39488) was analyzed to identify differentially expressed genes (DEGs). We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of DEGs. Gene set enrichment analysis (GSEA) was used to understand the potential activated signaling pathway. The protein–protein interaction (PPI) network was constructed with the STRING database and Cytoscape software. The Venn diagram between 10 hub genes and gene sets of 4 crucial signaling pathways was used to obtain core genes and relevant potential pathways. Furthermore, GSEAs were performed to understand their biological functions.Results: A total of 185 DEGs were screened in this study. The main biological function of the 111 upregulated genes in AV fistula primarily concentrated on cell proliferation and vascular remodeling, and the 74 downregulated genes in AV fistula were enriched in the biological function mainly relevant to inflammation. GSEA found four signaling pathways crucial for intimal hyperplasia, namely, MAPK, NOD-like, Cell Cycle, and TGF-beta signaling pathway. A total of 10 hub genes were identified, namely, EGR1, EGR2, EGR3, NR4A1, NR4A2, DUSP1, CXCR4, ATF3, CCL4, and CYR61. Particularly, DUSP1 and NR4A1 were identified as core genes that potentially participate in the MAPK signaling pathway. In AV fistula, the biological processes and pathways were primarily involved with MAPK signaling pathway and MAPK-mediated pathway with the high expression of DUSP1 and were highly relevant to cell proliferation and inflammation with the low expression of DUSP1. Besides, the biological processes and pathways in AV fistula with the high expression of NR4A1 similarly included the MAPK signaling pathway and the pathway mediated by MAPK signaling, and it was mainly involved with inflammation in AV fistula with the low expression of NR4A1.Conclusion: We screened four potential signaling pathways relevant to intimal hyperplasia and identified 10 hub genes, including two core genes (i.e., DUSP1 and NR4A1). Two core genes potentially participate in the MAPK signaling pathway and might serve as the therapeutic targets of intimal hyperplasia to prevent stenosis after AV fistula creation.

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The Expression and Prognostic Significance of the Nicotinic Receptor Cluster on 15q25 about CHRNA5 and PSMA4 mRNA in Lung Adenocarcinoma Utilizing TCGA Datasets

10.21203/rs.2.12982/v1 ◽

2019 ◽

Author(s):

Yuxiu Wang ◽

Xiaolin Wang ◽

Liping Wang ◽

Jianjun Gu ◽

Daohui Gong ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Excision Repair ◽

Prognostic Significance ◽

Enrichment Analysis ◽

High Expression ◽

Smoking History ◽

H1299 Cell ◽

Normal Tissues ◽

Impact On Survival ◽

Base Excision

Abstract Background: To explore the mutations expression and prognostic significance of 15q25 (CHRNA5 and PSMA4) mRNA in lung adenocarcinoma (LAC) based on immunohistochemistry, TCGA and bioinformatics.Methods: Mutations expression on chromosome 15q25 of 576 primary LAC patients was selected. And their survival and gene expression data were extracted from TCGA. The cell experiment about Beas-2b, A549 and H1299 cell lines were done to further prove the CHRNA5 and PSMA4 expression difference between lung cancer and normal cells. Immunohistochemistry data of CHRNA5 and PSMA4 were detected in LAC and normal tissues from 122 patients.Finally, Gene enrichment analysis (GSEA) was used to predict the regulatory genes of CHRNA5 and PSMA4.Results: CHRNA5 and PSMA4 are frequently mutated in the TCGA (CHRNA5, 1.7%; PSMA4, 1.3%).The expression of CHRNA5 and PSMA4 were obviously higher in A549 and H1299 cells. Immunohistochemical staining revealed that the level of CHRNA5 and PSMA4 was considerably higher in LAC group than in normal group. There was a significant association between high expression of CHRNA5 and Smoking History (P=0.011), Smoking History Pack Year Value(P=0.010). Besides, there was a significant correlation between CHRNA5 and PSMA4 expression level and prognosis (P=0.003; P=0.008),and the higher expression, the worse prognosis. GSEA results suggested that CHRNA5 and PSMA4 high expression samples were respectively enriched to cell cycle, base excision repair, oxidative phosphorylation, protein export, aminoacyl tRNA biosynthesis etc.Conclusions: The expression of CHRNA5 and PSMA4 mRNA has a significant impact on survival of LAC, they may be a potential target for treating patients with lung adenocarcinoma.

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