scholarly journals Minichromosome maintenance 6 complex component identified by bioinformatics analysis and experimental validation in esophageal squamous cell carcinoma

2020 ◽  
Vol 44 (3) ◽  
pp. 987-1002
Author(s):  
Xuebing Li ◽  
Zhenzhen Ren ◽  
Chao Xiong ◽  
Jie Geng ◽  
Yuqing Li ◽  
...  
2021 ◽  
Author(s):  
Zitong Feng ◽  
Jingge Qu ◽  
Xiao Liu ◽  
Jinghui Liang ◽  
Yongmeng Li ◽  
...  

Abstract Esophageal squamous cell carcinoma (ESCC) is a life-threatening thoracic tumor with a poor prognosis. Identifying the best-targeted therapy, appropriate biomarkers and individual treatment for patients with ESCC remains a significant challenge. The present study aimed to elucidate key candidate genes and immune cell infiltration characteristics in ESCC by integrated bioinformatics analysis. We downloaded nine gene expression datasets from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between ESCC tissues and normal tissues in each dataset were identified by the “limma” R package, and a total of 152 robust DEGs were identified by robust rank aggregation (RRA) algorithm. Functional enrichment analyses of the robust DEGs showed that these genes were significantly associated with extracellular matrix related process. Immune cell infiltration analysis was also conducted by CIBERSORT algorithm. We found that M0 and M1 macrophages were increased dramatically in ESCC while M2 macrophages decreased. Nine hub genes were picked out from a protein-protein interaction (PPI) network used by the CytoHubba plugin in Cytoscape. According to the receiver operating characteristic (ROC) curves and Kaplan-Meier survival analysis, the genes PLAU, SPP1 and VCAN had high diagnostic and prognostic values for ESCC patients. Based on univariate and multivariate regression analyses, seven genes (IL18, PLAU, ANO1, SLCO1B3, CST1, NELL2 and MAGEA11) from the robust DEGs were used to construct a good prognostic model. A nomogram that incorporates seven genes signature was established to develop a quantitative method for ESCC prognosis. Our results might provide aid for exploring potential therapeutic targets and prognosis evaluation in ESCC.


2020 ◽  
Vol 19 ◽  
pp. 153303382092096
Author(s):  
Yonghong Wang ◽  
Qimei Fang ◽  
Liru Tian ◽  
Zhongzhen Yuan ◽  
Lizhen Tian ◽  
...  

Background: In recent studies, microRNAs have been demonstrated as stable detectable biomarkers in blood for cancer. In addition, computer-aided biomarker discovery has now become an attractive paradigm for precision diagnosis. Methods: In this study, we identified and evaluated miR-139-3p as a biomarker for screening of esophageal squamous cell carcinoma using the Cancer Genome Atlas and Gene Expression Omnibus database analyses. We identified possible miR-139-3p target genes through the predicted database and esophageal squamous cell carcinoma upregulated genes from the Cancer Genome Atlas and Gene. Bioinformatics analysis was performed to determine key miR-139-3p targets and pathways associated with esophageal carcinoma. Finally, the expression and expected significance of hub genes were evaluated via the Genotype-Tissue Expression project. Results: MiR-139-3p was significantly downregulated in patients with esophageal squamous cell carcinoma/esophageal carcinoma. In GSE 122497, the area under the curve-receiver operating characteristic value, sensitivity, and specificity for serum miR-139-3p were 0.754, 67.49%, and 80.00%, respectively. The pattern specification process, skeletal system development, and regionalization process were the most enriched interactions in esophageal carcinoma. In addition, Epstein-Barr virus infection, human T-cell leukemia virus 1 infection, and human cytomegalovirus infection were identified as crucial pathways. Six hub genes (CD1A, FCGR2A, ANPEP, CD1B, membrane metalloendopeptidase, and TWIST1) were found, and FCGR2A and membrane metalloendopeptidase were further confirmed by genotype-tissue expression. High expression of membrane metalloendopeptidase correlated with a better overall survival but not with disease-free survival of patients with esophageal carcinoma. Conclusions: MiR-139-3p was identified as a candidate biomarker for predicting esophageal squamous cell carcinoma based on network analysis. MiR-139-3p acted as a tumor suppressor by targeting membrane metalloendopeptidase in esophageal carcinoma, and low expression of membrane metalloendopeptidase may indicate a better prognosis of patients with esophageal carcinoma.


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