scholarly journals Identification of Hub Gene GRIN1 Correlated with Histological Grade and Prognosis of Glioma by Weighted Gene Coexpression Network Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-22
Author(s):  
Aoran Yang ◽  
Xinhuan Wang ◽  
Yaofeng Hu ◽  
Chao Shang ◽  
Yang Hong

The function of glutamate ionotropic receptor NMDA type subunit 1 (GRIN1) in neurodegenerative diseases has been widely reported; however, its role in the occurrence of glioma remains less explored. We obtained clinical data and transcriptome data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Hub gene’s expression differential analysis and survival analysis were conducted by browsing the Gene Expression Profiling Interactive Analysis (GEPIA) database, Human Protein Atlas database, and LOGpc database. We conducted a variation analysis of datasets obtained from GEO and TCGA and performed a weighted gene coexpression network analysis (WGCNA) using the R programming language (3.6.3). Kaplan-Meier (KM) analysis was used to calculate the prognostic value of GRIN1. Finally, we conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Using STRING, we constructed a protein–protein interaction (PPI) network. Cytoscape software, a prerequisite of visualizing core genes, was installed, and CytoHubba detected the 10 most tumor-related core genes. We identified 185 differentially expressed genes (DEGs). GO and KEGG enrichment analyses illustrated that the identified DEGs are imperative in different biological functions and ascertained the potential pathways in which the DEGs may be enriched. The overall survival calculated by KM analysis showed that patients with lower expression of GRIN1 had worse prognoses than patients with higher expression of GRIN1 ( p = 0.004 ). The GEPIA and LOGpc databases were used to verify the expression difference of GRIN1 among GBM, LGG, and normal brain tissues. Ultimately, immunohistochemical assay results showed that GRIN1 was detected in normal tissue and not in the tumor specimens. Our results highlight a potential target for glioma treatment and will further our understanding of the molecular mechanisms underlying the treatment of glioma.

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Yong-Bo Chen ◽  
Liang Gao ◽  
Jin-Dong Zhang ◽  
Jiang Guo ◽  
Ping-Hong You ◽  
...  

Aim. This study is aimed at constructing the competing endogenous RNA (ceRNA) network in chromophobe renal cell carcinoma (ChRCC). Methods. Clinical and RNA sequence profiles of patients with ChRCC, including messenger RNAs (mRNAs), microRNAs (miRNAs), and long noncoding RNAs (lncRNAs), were obtained from The Cancer Genome Atlas (TCGA) database. “edgeR” and “clusterProfiler” packages were utilized to obtain the expression matrices of differential RNAs (DERNAs) and to conduct gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Weighted gene coexpression network analysis (WGCNA) was performed to screen the highly related RNAs, and miRcode, StarBase, miRTarBase, miRDB, and TargetScan datasets were used to predict the connections between them. Univariate and multivariate Cox proportional hazards regressions were performed in turn to elucidate prognosis-related mRNAs in order to construct the ceRNA regulatory network. Results. A total of 1628 DElncRNAs, 104 DEmiRNAs, and 2619 DEmRNAs were identified. WGCNA showed significant correlation in 1534 DElncRNAs, 98 DEmiRNAs, and 2543 DEmRNAs, which were related to ChRCC. Fourteen DEmiRNAs, 113 DElncRNAs, and 43 DEmRNAs were screened. Nine mRNAs (ALPL, ARHGAP29, CADM2, KIT, KLRD1, MYBL1, PSD3, SFRP1, and SLC7A11) significantly contributed to the overall survival (OS) of patients with ChRCC ( P < 0.05 ). Furthermore, two mRNAs (CADM2 and SFRP1) appeared to be independent risk factors for ChRCC. Conclusion. The findings revealed the molecular mechanism of ChRCC and potential therapeutic targets for the disease.


2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Qisheng Su ◽  
Qinpei Ding ◽  
Zunni Zhang ◽  
Zheng Yang ◽  
Yuling Qiu ◽  
...  

Background. Pheochromocytoma/paraganglioma (PCPG) is a benign neuroendocrine neoplasm in most cases, but metastasis and other malignant behaviors can be observed in this tumor. The aim of this study was to identify genes associated with the metastasis of PCPG. Methods. The Cancer Genome Atlas (TCGA) expression profile data and clinical information were downloaded from the cbioportal, and the weighted gene coexpression network analysis (WGCNA) was conducted. The gene coexpression modules were extracted from the network through the WGCNA package of R software. We further extracted metastasis-related modules of PCPG. Enrichment analysis of Biological Process of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes was carried out for important modules, and survival analysis of hub genes in the modules was performed. Results. A total of 168 PCPG samples were included in this study. The weighted gene coexpression network was constructed with 5125 genes of the top 25% variance among the 20501 genes obtained from the database. We identified 11 coexpression modules, among which the salmon module was associated with the age of PCPG patients at diagnosis, metastasis, and malignancy of the tumors. Conclusion. WGCNA was performed to identify the gene coexpression modules and hub genes in the metastasis-related gene module of PCPG. The findings in this study provide a new clue for further study of the mechanisms underlying the PCPG metastasis.


2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Zhenyuan Han ◽  
Huiping Ren ◽  
Jingjing Sun ◽  
Lihui Jin ◽  
Qin Wang ◽  
...  

Abstract Background Invasive malignant pleomorphic adenoma (IMPA) is a highly malignant neoplasm of the oral salivary glands with a poor prognosis and a considerable risk of recurrence. Many disease-causing genes of IMPA have been identified in recent decades (e.g., P53, PCNA and HMGA2), but many of these genes remain to be explored. Weighted gene coexpression network analysis (WGCNA) is a newly emerged algorithm that can cluster genes and form modules based on similar gene expression patterns. This study constructed a gene coexpression network of IMPA via WGCNA and then carried out multifaceted analysis to identify novel disease-causing genes. Methods RNA sequencing (RNA-seq) was performed for 10 pairs of IMPA and normal tissues to acquire the gene expression profiles. Differentially expressed genes (DEGs) were screened out with the cutoff criteria of |log2 Fold change (FC)|> 1 and adjusted p value  < 0.05. Then, WGCNA was applied to systematically identify the hidden diagnostic hub genes of IMPA. Results In this research, a total of 1970 DEGs were screened out in IMPA tissues, including 1056 upregulated DEGs and 914 downregulated DEGs. Functional enrichment analysis was performed for identified DEGs and revealed an enrichment of tumor-associated GO terms and KEGG pathways. We used WGCNA to identify gene module most relevant with the histological grade of IMPA. The gene FZD2 was then recognized as the hub gene of the selected module with the highest module membership (MM) value and intramodule connectivity in protein–protein interaction (PPI) network. According to immunohistochemistry (IHC) staining, the expression level of FZD2 was higher in low-grade IMPA than in high-grade IMPA. Conclusion FZD2 shows an expression dynamic that is negatively correlated with the clinical malignancy of IMPA and it plays a central role in the transcription network of IMPA. Thus, FZD2 serves as a promising histological indicator for the precise prediction of IMPA histological stages.


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Wei Liu ◽  
Yongquan Shi ◽  
Tao Cheng ◽  
Ruixue Jia ◽  
Ming-Zhong Sun ◽  
...  

In mouse models, the recovery of liver volume is mainly mediated by the proliferation of hepatocytes after partial hepatectomy that is commonly accompanied with ischemia-reperfusion. The identification of differently expressed genes in liver following partial hepatectomy benefits the better understanding of the molecular mechanisms during liver regeneration (LR) with appliable clinical significance. Briefly, studying different gene expression patterns in liver tissues collected from the mice group that survived through extensive hepatectomy will be of huge critical importance in LR than those collected from the mice group that survived through appropriate hepatectomy. In this study, we performed the weighted gene coexpression network analysis (WGCNA) to address the central candidate genes and to construct the free-scale gene coexpression networks using the identified dynamic different expressive genes in liver specimens from the mice with 85% hepatectomy (20% for seven-day survial rate) and 50% hepatectomy (100% for seven-day survial rate under ischemia-reperfusion condition compared with the sham group control mice). The WGCNA combined with Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses pinpointed out the apparent distinguished importance of three gene expression modules: the blue module for apoptotic process, the turquoise module for lipid metabolism, and the green module for fatty acid metabolic process in LR following extensive hepatectomy. WGCNA analysis and protein-protein interaction (PPI) network construction highlighted FAM175B, OGT, and PDE3B were the potential three hub genes in the previously mentioned three modules. This work may help to provide new clues to the future fundamental study and treatment strategy for LR following liver injury and hepatectomy.


2019 ◽  
Vol 49 (10) ◽  
pp. 1195-1206 ◽  
Author(s):  
Aiping Tian ◽  
Ke Pu ◽  
Boxuan Li ◽  
Min Li ◽  
Xiaoguang Liu ◽  
...  

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