scholarly journals Investigation of Candidate Genes and Mechanism Associated with Immune Cell during the Progression of Glioblastoma based on Bioinformatics

2020 ◽  
Author(s):  
Hui Xie ◽  
Xiao-hui Ding ◽  
Ce Yuan ◽  
Jin-jiang Li ◽  
Zhao-yang Li ◽  
...  
Keyword(s):  
Immune Cell ◽  
Risk Model ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Normal Group ◽  
Functional Enrichment ◽  
M2 Macrophage ◽  
Survival Prognosis ◽  
Cerna Network ◽  
Tumor Group

Abstract Background: This study aimed to investigate the molecular mechanism of immune cell infiltration during the development of glioblastoma multiforme (GBM), and explore the potential immune cell associated prognostic genes for GBM. Methods: Gene expression data and corresponding clinical data of GBM samples (tumor group) and normal samples (normal group) in TCGA-GBM and GTEx dataset were downloaded. The differentially expression analysis was performed on samples between two groups. Based on tumor immune microenvironment analysis, the immune-related RNAs (lncRNAs and mRNAs) were further explored. Then, functional enrichment analysis, ceRNA network, risk prediction model and prognosis investigation were performed. Finally, the results of survival prognosis of key genes were tested by additional datasets. Results: A total of 4989 up-regulated genes and 2349 down-regulated genes were revealed between tumor group and normal group. M2 macrophages accounted for the largest proportion of tumor infiltrates immune cells in GBM, and was related to the prognosis of GBM patients. Totally 168 mRNAs (KIF18B) and 5 lncRNAs were related to infiltration of M2 Macrophage, of which 25 mRNAs and 5 lncRNAs forms a ceRNA network through 37 miRNAs (eg., miR-6849-3p). These genes were mainly assembled in functions like signal release. A risk model based on 5 mRNAs (such as FOX4 and ELFN2) and lncRNA PR11-161H23.5 was constructed. Verification test showed that all 5 mRNAs were significantly associated with OS prognosis.Conclusions: M2 Macrophage infiltration might participate in tumorigenesis of GBM via RP11-161H23.5-miR6849-3p-KIF18B ceRNA interaction. Furthermore, mRNAs such as FOX4 and ELFN2 might be potential prognostic markers for GBM patients.

scholarly journals Competitive Endogenous RNA (ceRNA) Regulation Network of lncRNA–miRNA–mRNA in wilms tumor

2019 ◽  
Author(s):  
fucai tang ◽  
zechao Lu ◽  
jiamin wang ◽  
zhibiao Li ◽  
weijia Wu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Regulatory Network ◽  
Wilms Tumor ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Survival Prognosis ◽  
Cerna Network ◽  
Competitive Endogenous Rna

Abstract Background Competitive endogenous RNA (ceRNA) have revealed a new mechanism of interaction between RNAs. However, such comprehension of the ceRNA regulatory network in wilms tumor remains limited. Methods Raw RNA sequencing profiles regarding mRNAs, miRNAs and lncRNAs on wilms tumor samples and normal samples were obtained from Therapeutically Applicable Research to Generate Effective Treatment (TARGET). EdgeR package was applied to identify differentially expressed lncRNAs, miRNAs and mRNAs. Functional enrichment analysis were conducted via DAVID database and the ClusterProfile R package. The lncRNA–miRNA–mRNA interaction ceRNA network was established in Cytoscape according to the identified lncRNAs–miRNAs and miRNAs–mRNAs interactions. Subsequently, correlation between ceRNA network and overall survival prognosis were analyzed. Results A total of 2,037 lncRNAs, 154 miRNAs and 3,609 mRNAs were identified as differentially expressed RNAs in wilms tumor. 205 lncRNAs, 26 miRNAs and 143 mRNAs were included in ceRNA regulatory network. Analysis results showed that 14 out of the 205 lncRNAs, 1 out of 26 miRNAs and 8 out of 143 mRNAs were associated with overall survival in wilms tumor patients (P < 0.05). Conclusions CeRNA networks played an important role in wilms tumor. This might provide effective bioinformatics basis and novel insights for further understanding of the mechanisms underlying wilms tumor.

scholarly journals Identification of novel biomarkers and prognostic value of the location (head, body, or tail) of pancreatic cancer

2019 ◽  
Author(s):  
Shuwen Han ◽  
Xi Yang ◽  
Jiamin Xu ◽  
Wei Wu ◽  
Jin Liu
Keyword(s):  
Pancreatic Cancer ◽  
Risk Model ◽  
Pancreatic Head ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Multivariate Regression Analysis ◽  
Functional Enrichment ◽  
Expression Data ◽  
Pancreatic Head Cancer ◽  
Cerna Network

Abstract Objective : This study was designed to identify the differentially expressed mRNA, microRNA (miRNA), and long non-coding RNA (lncRNA) and their functions in pancreatic cancer (PC). Methods: The expression data of PC and normal samples were downloaded from the GEO database. The expression data of pancreatic head (H), body (B), and tail (T) were downloaded from the TCGA database. After data preprocessing, the differential analyses between PC vs. Normal, H vs. B, H vs. T, and T vs. B were performed. Overlapping genes between PC vs. Normal and the different locations (the union of genes among T vs. B, T vs. H, and B vs. H) were selected. The competing endogenous RNAs (ceRNA) network was constructed based on co-expression analysis and prediction of targets, followed by functional enrichment analysis. Construction of an mRNA prognosis risk model and screening of prognostic factors were performed using Cox univariate/multivariate regression analysis, followed by Nomogram model construction. Finally, the gene-drug interactions were predicted for the DE-mRNA. Results: A five-mRNA prognostic model (GRHL2+CACNA1A+GRM1+UPK1B+PKHD1) was constructed, and the risk score was relatively increased with the increased expression of the GRHL2, PKHD1, and UPK1B, and the decreased expression of CACNA1A and GRM1. Compared with pancreatic body/tail cancer, the expression of GRHL2 was increased, while the expression of CACNA1A and GRM1 was decreased in pancreatic head cancer. LncRNA AC006369.2-miR-146a-5p-CACNA1A/GRM1 was a regulatory axis in the ceRNA network. Verapamil was predicted to be an antagonist of CACNA1A. Conclusion: Our results provide a new direction for the accurate diagnosis and treatment of PC and for investigating the mechanism of PC.

scholarly journals LnCeVar: a comprehensive database of genomic variations that disturb ceRNA network regulation

2019 ◽  
Author(s):  
Peng Wang ◽  
Xin Li ◽  
Yue Gao ◽  
Qiuyan Guo ◽  
Shangwei Ning ◽  
...  
Keyword(s):  
Cox Regression ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Data Sets ◽  
Genomic Variations ◽  
Cancer Hallmarks ◽  
Cerna Network ◽  
Comprehensive Database ◽  
User Friendly

Abstract LnCeVar (http://www.bio-bigdata.net/LnCeVar/) is a comprehensive database that aims to provide genomic variations that disturb lncRNA-associated competing endogenous RNA (ceRNA) network regulation curated from the published literature and high-throughput data sets. LnCeVar curated 119 501 variation–ceRNA events from thousands of samples and cell lines, including: (i) more than 2000 experimentally supported circulating, drug-resistant and prognosis-related lncRNA biomarkers; (ii) 11 418 somatic mutation–ceRNA events from TCGA and COSMIC; (iii) 112 674 CNV–ceRNA events from TCGA; (iv) 67 066 SNP–ceRNA events from the 1000 Genomes Project. LnCeVar provides a user-friendly searching and browsing interface. In addition, as an important supplement of the database, several flexible tools have been developed to aid retrieval and analysis of the data. The LnCeVar–BLAST interface is a convenient way for users to search ceRNAs by interesting sequences. LnCeVar–Function is a tool for performing functional enrichment analysis. LnCeVar–Hallmark identifies dysregulated cancer hallmarks of variation–ceRNA events. LnCeVar–Survival performs COX regression analyses and produces survival curves for variation–ceRNA events. LnCeVar–Network identifies and creates a visualization of dysregulated variation–ceRNA networks. Collectively, LnCeVar will serve as an important resource for investigating the functions and mechanisms of personalized genomic variations that disturb ceRNA network regulation in human diseases.

scholarly journals Integrated analysis identifies a pathway-related competing endogenous RNA network in the progression of pancreatic cancer

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Fuqiang Zu ◽  
Peng Liu ◽  
Huaitao Wang ◽  
Ting Zhu ◽  
Jian Sun ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Tumor Formation ◽  
Functional Enrichment ◽  
Integrated Analysis ◽  
Competing Endogenous Rna ◽  
Hub Genes ◽  
Cerna Network ◽  
Competing Endogenous Rna Network

Abstract Background It is well acknowledged that cancer-related pathways play pivotal roles in the progression of pancreatic cancer (PC). Employing Integrated analysis, we aim to identify the pathway-related ceRNA network associated with PC progression. Methods We divided eight GEO datasets into three groups according to their platform, and combined TCGA and GTEx databases as a group. Additionally, we screened out the differentially expressed genes (DEGs) and performed functional enrichment analysis in each group, and recognized the top hub genes in the most enriched pathway. Furthermore, the upstream of miRNAs and lncRNAs were predicted and validated according to their expression and prognostic roles. Finally, the co-expression analysis was applied to identify a pathway-related ceRNA network in the progression of PC. Results A total of 51 significant pathways that common enriched in all groups were spotted. Enrichment analysis indicated that pathway in cancer was greatly linked with tumor formation and progression. Next, the top 20 hug genes in this pathway were recognized, and stepwise prediction and validation from mRNA to lncRNA, including 11 hub genes, 4 key miRNAs, and 2 key lncRNAs, were applied to identify a meaningful ceRNA network according to ceRNA rules. Ultimately, we identified the PVT1/miR-20b/CCND1 axis as a promising pathway-related ceRNA axis in the progression of PC. Conclusion Overall, we elucidate the pathway-related ceRNA regulatory network of PVT1/miR-20b/CCND1 in the progression of PC, which can be considered as therapeutic targets and encouraging prognostic biomarkers for PC.

scholarly journals SPP1 is a Prognostic Related Biomarker and Correlated With Tumor-Infiltrating Immune Cells in Ovarian Cancer

2021 ◽  
Author(s):  
Wen Gao ◽  
Sheng Yin ◽  
Haiyan Sun ◽  
Zhuyan Shao ◽  
Peipei Shi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Vital Role ◽  
Functional Enrichment ◽  
Immune Infiltration ◽  
Kaplan Meier ◽  
Secreted Phosphoprotein 1

Abstract Background: Secreted phosphoprotein 1 (SPP1) plays a vital role in tumor progression of some cancer types, but little is known whether it is a bystander or an actual player on driving immune infiltration in ovarian cancer.Methods: In this study, the expression of SPP1 was identified by Oncomine, GEPIA and TIMER databases, and SPP1 immumohistochemical staining analysis was assessed by The HPA database. The clinical outcomes between SPP1 expression and ovarian cancer patients were evaluated via Kaplan-Meier Plotter and PrognoScan dataset. Immune infiltration analyses were explored using TIMER and TISIDB dataset. In addition, Functional enrichment analyses were performed with Metascape and GeneMANIA database.Results: SPP1 was found overexpressed in ovarian tumor tissues and high SPP1 expression was correlated with shorter OS and PFS survivals. Particularly, elevated SPP1 expression was significantly associated with stage III ovarian cancer. Notably, SPP1 expression was positively correlated with infiltrating levels of CD4+ T cells, CD8+ T cells, macrophages, neutrophils, and dendritic cells. Furthermore, SPP1 expression showed strong correlations with diverse immune hallmark sets in ovarian cancer. Of particular importance, functional enrichment analysis suggested that SPP1 strong related with immune response.Conclusions: These findings imply that SPP1 is correlated with prognosis and immune cell infiltrating, offering a new potential immunotherapeutic target in ovarian cancer.Trial registration: Not applicable.

scholarly journals Comprehensive Analysis of the Prognostic Value and Immune Infiltration of Calpains in Pancreatic Cancer

2021 ◽  
Author(s):  
Lan Chuan ◽  
Haoyou Tang ◽  
Sheng Liu ◽  
Lin Ma ◽  
Yifu Hou
Keyword(s):  
Pancreatic Cancer ◽  
Immune Cell ◽  
Treatment Strategies ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Cell Surface Receptor ◽  
Cell Junction ◽  
Expression Levels ◽  
Surface Receptor

Abstract Background: Calpains (CAPNs) are intracellular calcium-activated neutral cysteine proteinases that are involved in cancer initiation, progression, and metastasis; however, their role in pancreatic cancer (PC) remains unclear. Methods: We combined data from various mainstream databases (i.e., Oncomine, GEPIA, Kaplan-Meier plotter, cBioPortal, STRING, GeneMANIA, and ssGSEA) and investigated the role of CAPNs in the prognosis of PC and immune cell infiltration.Results: Our results showed that CAPN1, 2, 4, 5, 6, 8, 9, 10, and 12 were highly expressed in PC. The expression levels of CAPN1, 5, 8, and 12 were positively correlated with the individual cancer stages. Moreover, the expression levels of CAPN1, 2, 5, and 8 were negatively correlated with the overall survival (OS) and recurrence-free survival (RFS); whereas that of CAPN10 was positively correlated with OS and RFS. We found that CAPN1, 2, 5, and 8 were correlated with tumour-infiltrating T follicular helper cells and CAPN10 with tumour-infiltrating T helper 2 cells. Functional enrichment analysis showed that the differentially expressed CAPNs (CAPN1, 2, 5, 8, and 10) are involved in axonogenesis, cell-substrate adhesion, immune response-activating cell surface receptor signalling pathway, and cell junction organisation in PC.Conclusions: These results suggested that CAPN1, 2, 5, 8, and 10 could be used as prognostic biomarkers in PC and can assist in improving individualised treatment strategies.

scholarly journals Differentially Expressed Functional LncRNAs in Human Subjects With Metabolic Syndrome Reflect a Competing Endogenous RNA Network in Circulating Extracellular Vesicles

2021 ◽  
Vol 8 ◽  
Author(s):  
Yongxin Li ◽  
Yu Meng ◽  
Yuanhang Liu ◽  
Andre J. van Wijnen ◽  
Alfonso Eirin ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Extracellular Vesicles ◽  
Disease Risk ◽  
Human Subjects ◽  
Inflammatory Marker ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Cerna Network

Metabolic syndrome (MetS), a collective cluster of disease risk factors that include dyslipidemia, obesity, inflammation, hypertension, and insulin resistance, affects numerous people worldwide. Accumulating studies have shown that long non-coding RNAs (lncRNAs) serve as competing endogenous RNAs (ceRNAs) to play essential roles in regulating gene expression in various diseases. To explore the role of lncRNAs as ceRNAs in MetS, we examined a MetS-associated network in circulating extracellular vesicles (EVs) collected from the systemic blood of MetS and control patients (n = 5 each). In total, 191 differentially expressed lncRNAs, 1,389 mRNAs, and 138 miRNAs were selected for further analysis. Biological processes and pathway functional enrichment analysis were performed based on the Database for Annotation, Visualization, and Integrated Discovery (DAVID). The lncRNA/mRNA/miRNA ceRNA network was constructed by Cytoscape v3.8 based on the DE-RNAs and included 13 lncRNAs, 8 miRNAs, and 64 mRNAs. MetS patients showed elevated body weight, glucose, blood pressure, insulin, liver injury, and inflammatory marker levels. We found that lncRNAs reflect a ceRNA network that may regulate central cellular processes and complications of MetS, including cancer. These findings suggest that MetS alters the interactions among the ceRNA network components in circulating EVs and that this cargo of circulating EVs may have potential translational ramifications for MetS.

scholarly journals Integrated analysis identifies a pathway-related competing endogenous RNA network in the progression of Pancreatic cancer

2020 ◽  
Author(s):  
Fuqiang Zu ◽  
Peng Liu ◽  
Huaitao Wang ◽  
Ting Zhu ◽  
Jian Sun ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Tumor Formation ◽  
Functional Enrichment ◽  
Integrated Analysis ◽  
Competing Endogenous Rna ◽  
Hub Genes ◽  
Cerna Network ◽  
Competing Endogenous Rna Network

Abstract Background: It is well acknowledged that cancer-related pathways play pivotal roles in the progression of pancreatic cancer (PC). Employing Integrated analysis, we aim to identify the pathway-related ceRNA network associated with PC progression.Methods: We divided eight GEO datasets into three groups according to their platform, and combined TCGA and GTEx databases as a group. Additionally, we screened out the differentially expressed genes (DEGs) and performed functional enrichment analysis in each group, and recognized the top hub genes in the most enriched pathway. Furthermore, the upstream of miRNAs and lncRNAs were predicted and validated according to their expression and prognostic roles. Finally, the co-expression analysis was applied to identify a pathway-related ceRNA network in the progression of PC.Results: A total of 51 significant pathways that common enriched in all groups were spotted. Enrichment analysis indicated that pathway in cancer was greatly linked with tumor formation and progression. Next, the top 20 hug genes in this pathway were recognized, and stepwise prediction and validation from mRNA to lncRNA, including 11 hub genes, 4 key miRNAs, and 2 key lncRNAs, were applied to identify a meaningful ceRNA network according to ceRNA rules. Ultimately, we identified the PVT1/miR-20b-/CCND1 axis as a promising pathway-related ceRNA axis in the progression of PC.Conclusion: Overall, we elucidate the pathway-related ceRNA regulatory network of PVT1/miR-20b-/CCND1 in the progression of PC, which can be considered as therapeutic targets and encouraging prognostic biomarkers for PC.

scholarly journals Construction and Analysis of Survival-Associated Competing Endogenous RNA Network in Lung Adenocarcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Lixian Chen ◽  
Zhonglu Ren ◽  
Yongming Cai
Keyword(s):  
Prognostic Factors ◽  
Lung Adenocarcinoma ◽  
Molecular Mechanisms ◽  
Cox Regression ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Competing Endogenous Rna ◽  
Cox Regression Analysis ◽  
Cerna Network

Increasing evidence has shown that noncoding RNAs play significant roles in the initiation, progression, and metastasis of tumours via participating in competing endogenous RNA (ceRNA) networks. However, the survival-associated ceRNA in lung adenocarcinoma (LUAD) remains poorly understood. In this study, we aimed to investigate the regulatory mechanisms underlying ceRNA in LUAD to identify novel prognostic factors. mRNA, lncRNA, and miRNA sequencing data obtained from the GDC data portal were utilized to identify differentially expressed (DE) RNAs. Survival-related RNAs were recognized using univariate Kaplan-Meier survival analysis. We performed functional enrichment analysis of survival-related mRNAs using the clusterProfiler package of R and STRING. lncRNA-miRNA and miRNA-mRNA interactions were predicted based on miRcode, Starbase, and miRanda. Subsequently, the survival-associated ceRNA network was constructed for LUAD. Multivariate Cox regression analysis was used to identify prognostic factors. Finally, we acquired 15 DE miRNAs, 49 DE lncRNAs, and 843 DE mRNAs associated with significant overall survival. Functional enrichment analysis indicated that survival-related DE mRNAs were enriched in cell cycle. The survival-associated lncRNA-miRNA-mRNA ceRNA network was constructed using five miRNAs, 49 mRNAs, and 21 lncRNAs. Furthermore, seven hub RNAs (LINC01936, miR-20a-5p, miR-31-5p, TNS1, TGFBR2, SMAD7, and NEDD4L) were identified based on the ceRNA network. LINC01936 and miR-31-5p were found to be significant using the multifactorial Cox regression model. In conclusion, we successfully constructed a survival-related lncRNA-miRNA-mRNA ceRNA regulatory network in LUAD and identified seven hub RNAs, which provide novel insights into the regulatory molecular mechanisms associated with survival of LUAD, and identified two independent prognostic predictors for LUAD.

scholarly journals Comprehensive Analysis of Aquaporin Superfamily in Lung Adenocarcinoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Guofu Lin ◽  
Luyang Chen ◽  
Lanlan Lin ◽  
Hai Lin ◽  
Zhifeng Guo ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Functional Enrichment Analysis ◽  
Tumor Stage ◽  
Stage I ◽  
Functional Enrichment ◽  
Gene Expressions ◽  
Kaplan Meier

Background: Lung adenocarcinoma (LUAD) is the most predomintnt lung cancer subtype with increasing morbidity and mortality. Previous studies have shown that aquaporin (AQP) family genes were correlated with tumor progression and metastasis in several kinds of malignancies. However, their biological behaviors and prognostic values in LUAD have not been comprehensively elucidated.Methods: RNA sequencing and real-time reverse transcription PCR (RT-PCR) were used to assess AQP1/3/4/5 gene expressions in LUAD patients using GEPIA and UALCAN databases. And then Kaplan–Meier analysis, cBioPortal, Metascape, GeneMANIA, TISIDB, and TIMER were utilized to determine the prognostic value, mutation frequency, and immune cell infiltration of AQP family members in LUAD.Results: We found that AQP3 expression was significantly elevated and AQP1 expression was markedly reduced in LUAD patients, whereas the expression levels of AQP4 and AQP5 exhibited no significant changes. The Kaplan–Meier survival analysis indicated that the higher expressions of AQP1/4/5 were related to longer overall survival (OS). Of interest, AQP3 was significantly correlated with the clinical tumor stage and lower AQP3 expression showed favorable prognosis in stage I LUAD patients, which indicated that AQP3 may be a potential prognostic biomarker for patients. Through functional enrichment analysis, the functions of these four AQPs genes were mainly involved in the passive transport by aquaporins, water homeostasis, and protein tetramerization. Moreover, AQP1/3/4/5 expression was strongly associated with tumor-infiltrating lymphocytes (TILs) in LUAD.Conclusion: AQP3 can be used as a prognosis and survival biomarker for stage I LUAD. These findings may provide novel insights into developing molecular targeted therapies in LUAD.

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