scholarly journals Identifying Tumorigenesis and Prognosis-Related Genes of Lung Adenocarcinoma: Based on Weighted Gene Coexpression Network Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Ming Yi ◽  
Tianye Li ◽  
Shuang Qin ◽  
Shengnan Yu ◽  
Qian Chu ◽  
...  

Lung adenocarcinoma is the most frequently diagnosed subtype of nonsmall cell lung cancer. The molecular mechanisms of the initiation and progression of lung adenocarcinoma remain to be further determined. This study aimed to screen genes related to the progression of lung adenocarcinoma. By weighted gene coexpression network analysis (WGCNA), we constructed a free-scale gene coexpression network to evaluate the correlations between multiple gene sets and patients’ clinical traits, then further identify predictive biomarkers. GSE11969 was obtained from the Gene Expression Omnibus (GEO) database which contained the gene expression data of 90 lung adenocarcinoma patients. Data of the Cancer Genome Atlas (TCGA) were employed as the validation cohort. After the average linkage hierarchical clustering, a total of 9 modules were generated. In the clinical significant module (R = 0.44, P<0.0001), we identified 29 network hub genes. Subsequent verification in the TCGA database showed that 11 hub genes (ANLN, CDCA5, FLJ21924, LMNB1, MAD2L1, RACGAP1, RFC4, SNRPD1, TOP2A, TTK, and ZWINT) were significantly associated with poor survival data of lung adenocarcinomas. Besides, the results of receiver operating characteristic curves indicated that the mRNA levels of this group of genes exhibited high specificity and sensitivity to distinguish malignant lesions from nonmalignant tissues. Apart from mRNA levels, we found that the protein abundances of these 11 genes were remarkably upregulated in lung adenocarcinomas compared with normal tissues. In conclusion, by the WGCNA method, a panel of 11 genes were identified as predictive biomarkers for tumorigenesis and poor prognosis of lung adenocarcinomas.

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

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Baiyang Yu ◽  
Jianbin Liu ◽  
Di Wu ◽  
Ying Liu ◽  
Weijian Cen ◽  
...  

An amendment to this paper has been published and can be accessed via the original article.


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. 1-13
Author(s):  
Mi Zhou ◽  
Ruru Guo ◽  
Yong-Fei Wang ◽  
Wanling Yang ◽  
Rongxiu Li ◽  
...  

Systemic juvenile idiopathic arthritis (sJIA) is a severe autoinflammatory disorder with a still not clearly defined molecular mechanism. To better understand the disease, we used scattered datasets from public domains and performed a weighted gene coexpression network analysis (WGCNA) to identify key modules and hub genes underlying sJIA pathogenesis. Two gene expression datasets, GSE7753 and GSE13501, were used to construct the WGCNA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were applied to the genes and hub genes in the sJIA modules. Cytoscape was used to screen and visualize the hub genes. We further compared the hub genes with the genome-wide association study (GWAS) genes and used a consensus WGCNA to verify that our conclusions were conservative and reproducible across multiple independent datasets. A total of 5,414 genes were obtained for WGCNA, from which highly correlated genes were divided into 17 modules. The red module demonstrated the highest correlation with the sJIA module ( r = 0.8 , p = 3 e − 29 ), whereas the green-yellow module was found to be closely related to the non-sJIA module ( r = 0.62 , p = 1 e − 14 ). Functional enrichment analysis demonstrated that the red module was mostly enriched in the activation of immune responses, infection, nucleosomes, and erythrocytes, and the green-yellow module was mostly enriched in immune responses and inflammation. Additionally, the hub genes in the red module were highly enriched in erythrocyte differentiation, including ALAS2, AHSP, TRIM10, TRIM58, and KLF1. The hub genes from the green-yellow module were mainly associated with immune responses, as exemplified by the genes KLRB1, KLRF1, CD160, and KIRs. We identified sJIA-related modules and several hub genes that might be associated with the development of sJIA. Particularly, the modules may help understand the mechanisms of sJIA, and the hub genes may become biomarkers and therapeutic targets of sJIA in the future.


PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8843
Author(s):  
Dongmei Guo ◽  
Hongchun Wang ◽  
Li Sun ◽  
Shuang Liu ◽  
Shujing Du ◽  
...  

Purpose Mantle cell lymphoma (MCL) is a rare and aggressive subtype of non-Hodgkin lymphoma that is incurable with standard therapies. The use of gene expression analysis has been of interest, recently, to detect biomarkers for cancer. There is a great need for systemic coexpression network analysis of MCL and this study aims to establish a gene coexpression network to forecast key genes related to the pathogenesis and prognosis of MCL. Methods The microarray dataset GSE93291 was downloaded from the Gene Expression Omnibus database. We systematically identified coexpression modules using the weighted gene coexpression network analysis method (WGCNA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis were performed on the modules deemed important. The protein–protein interaction networks were constructed and visualized using Cytoscape software on the basis of the STRING website; the hub genes in the top weighted network were identified. Survival data were analyzed using the Kaplan–Meier method and were compared using the log-rank test. Results Seven coexpression modules consisting of different genes were applied to 5,000 genes in the 121 human MCL samples using WGCNA software. GO and KEGG enrichment analysis identified the blue module as one of the most important modules; the most critical pathways identified were the ribosome, oxidative phosphorylation and proteasome pathways. The hub genes in the top weighted network were regarded as real hub genes (IL2RB, CD3D, RPL26L1, POLR2K, KIF11, CDC20, CCNB1, CCNA2, PUF60, SNRNP70, AKT1 and PRPF40A). Survival analysis revealed that seven genes (KIF11, CDC20, CCNB1, CCNA2, PRPF40A, CD3D and PUF60) were associated with overall survival time (p < 0.05). Conclusions The blue module may play a vital role in the pathogenesis of MCL. Five real hub genes (KIF11, CDC20, CCNB1, CCNA2 and PUF60) were identified as potential prognostic biomarkers as well as therapeutic targets with clinical utility for MCL.


Genome ◽  
2020 ◽  
Vol 63 (11) ◽  
pp. 561-575
Author(s):  
Hui Zhang ◽  
Dan Yang ◽  
Siliang Chen ◽  
Fangda Li ◽  
Liqiang Cui ◽  
...  

Proteases are involved in the degradation of the extracellular matrix (ECM), which contributes to the formation of abdominal aortic aneurysm (AAA). To identify new disease targets in addition to the results of previous microarray studies, we performed next-generation sequencing (NGS) of the whole transcriptome of Angiotensin II-treated ApoE−/− male mice (n = 4) and control mice (n = 4) to obtain differentially expressed genes (DEGs). Identified DEGs of proteases were analyzed using weighted gene coexpression network analysis (WGCNA). RT-qPCR was conducted to validate the differential expression of selected hub genes. We found that 43 DEGs were correlated with the expression of the protease profile, and most were clustered in immune response module. Among 26 hub genes, we found that Mmp16 and Mmp17 were significantly downregulated in AAA mice, while Ctsa, Ctsc, and Ctsw were upregulated. Our functional annotation analysis of genes coexpressed with the five hub genes indicated that Ctsw and Mmp17 were involved in T cell regulation and Cell adhesion molecule pathway, respectively, and that both were involved in general regulation of the cell cycle and gene expression. Overall, our data suggest that these ectopic genes are potentially crucial to AAA formation and may act as biomarkers for the diagnosis of AAA.


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.


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