scholarly journals Identification of Prognostic Candidate Genes in Breast Cancer by Integrated Bioinformatic Analysis

2019 ◽  
Vol 8 (8) ◽  
pp. 1160 ◽  
Author(s):  
Wang ◽  
Li ◽  
Cai ◽  
Sheu ◽  
Tsai ◽  
...  

Breast cancer is one of the most common malignancies. However, the molecular mechanisms underlying its pathogenesis remain to be elucidated. The present study aimed to identify the potential prognostic marker genes associated with the progression of breast cancer. Weighted gene coexpression network analysis was used to construct free-scale gene coexpression networks, evaluate the associations between the gene sets and clinical features, and identify candidate biomarkers. The gene expression profiles of GSE48213 were selected from the Gene Expression Omnibus database. RNA-seq data and clinical information on breast cancer from The Cancer Genome Atlas were used for validation. Four modules were identified from the gene coexpression network, one of which was found to be significantly associated with patient survival time. The expression status of 28 genes formed the black module (basal); 18 genes, dark red module (claudin-low); nine genes, brown module (luminal), and seven genes, midnight blue module (nonmalignant). These modules were clustered into two groups according to significant difference in survival time between the groups. Therefore, based on betweenness centrality, we identified TXN and ANXA2 in the nonmalignant module, TPM4 and LOXL2 in the luminal module, TPRN and ADCY6 in the claudin-low module, and TUBA1C and CMIP in the basal module as the genes with the highest betweenness, suggesting that they play a central role in information transfer in the network. In the present study, eight candidate biomarkers were identified for further basic and advanced understanding of the molecular pathogenesis of breast cancer by using co-expression network analysis.

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. 1-22
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. 1-12
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.


Complexity ◽  
2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Xin Chen ◽  
Zuyuan Yang ◽  
Chao Yang ◽  
Kan Xie ◽  
Weijun Sun ◽  
...  

Predictive and prognostic biomarkers facilitate the selection of treatment strategies that can improve the survival of patients. Accumulating evidence indicates that long noncoding RNAs (lncRNAs) play important roles in cancer progression, with diagnostic and prognostic potential. However, few prognostic lncRNAs are reported for breast cancer, and little is known about their functions that contribute to cancer pathogenesis. In this paper, we used weighted correlation network analysis (WGCNA) to construct networks containing noncoding and protein-coding genes based on their expression in 1097 breast cancer patients. The differentially expressed genes were significantly overlapped with gene modules regulating cell cycle and cell adhesion. The cell cycle-related lncRNAs were consistently downregulated in breast cancer. One lncRNA, EIF3J-AS1, is significantly associated with clinicopathological characteristics, including tumor size, lymph node metastasis, estrogen receptor (ER), and progesterone receptor (PR) status. Kaplan–Meier survival analysis revealed that EIF3J-AS1, a downregulated lncRNA in breast tumor, is a potential prognostic marker for breast cancer. EIF3J-AS1 may function in an estrogen-independent manner and could be inhibited by the compound FDI-6. Therefore, integrating sparse gene coexpression network and clinicopathological features can accelerate identification and functional characterization of novel prognostic lncRNAs in breast cancer.


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