Identification of key genes and pathways in benign prostatic hyperplasia

Ke, Zhi‐Bin; Cai, Hai; Wu, Yupeng; Lin, Yunzhi; Li, Xiaodong; Huang, Jiaofeng; Sun, Xiong‐Lin; Zheng, Qing‐Shui; Xue, Xue-Yi; Wei, Yong; Xu, Ning

doi:10.1002/jcp.28592

Cited by 33 publications

(26 citation statements)

References 31 publications

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“…Qiu et al [31] demonstrated the regulation role of tumor-associated macrophages in BCa cell growth. Xue et al [32] also indicated that the infiltration of M2 macrophage might be an underlying target of immunotherapy for BCa patients. Previous studies have demonstrated that tumor-infiltrating T cell landscape in bladder cancer would contribute to management decisions making, particularly immunotherapy [33].…”

Section: Discussionmentioning

confidence: 99%

Development and validation of a molecular prognostic index of bladder cancer based on immunogenomic landscape analysis

Lin

et al. 2020

Cancer Cell Int

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Background: Bladder cancer (BCa) is one of the important tumors that have been proven to be treatable with immunotherapy. This study aims to identify and validate a molecular prognostic index of BCa based on immunogenomic landscape analysis. Methods: The cancer genome atlas (TCGA) database and immunology database and analysis portal (ImmPort) database were used to identified differentially expressed immune-related genes (IRGs). Prognostic IRGs were screened and protein-protein interaction (PPI) network was constructed. Multivariate Cox analysis was performed to develop a molecular prognostic index of BCa. Internal and external validation were then performed in TCGA cohort and GEO cohort, respectively. Besides, we also explore the relationship between this index and clinical characteristics, immune cell infiltration and tumor microenvironment. Results: A total of 61 prognostic IRGs were identified and a molecular prognostic index was developed. The top four hub genes included MMP9, IGF1, CXCL12 and PGF. The difference in overall survival between high-risk group and low-risk group was statistically significant. The area under curve of the receiver operating characteristic (ROC) curve was 0.757, suggesting the potential for this index. Besides, Internal validation using TCGA cohort and external validation using GEO cohort indicated that this index was of great performance in predicting outcome. T cells CD8, T cells CD4 memory activated, T cells follicular helper, macrophages M0, macrophages M2 and neutrophils were significantly associated with prognosis of BCa patients. Female, high grade, stage III&IV, N1-3 and T3-4 were associated significantly with higher risk score compared with male, low grade, stage I&II, N0 and T1-2, respectively. High risk score had a positive association with higher stromal score and ESTIMATE score while high risk score had a negative association with tumor purity. Conclusions: This study identified several prognostic immune-related genes of clinical value. Besides, we developed and validated a molecular index based on immunogenomic landscape analysis, which performed well in predicting prognosis of BCa. Further researches are needed to verify the effectiveness of this index and these vital genes.

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Section: Discussionmentioning

confidence: 99%

Development and validation of a molecular prognostic index of bladder cancer based on immunogenomic landscape analysis

Lin

et al. 2020

Cancer Cell Int

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“…The DAVID online tool (https://david.ncifcrf.gov/) was used to annotate the survival‐related mRNAs as previously described (Ke et al, ; Xu et al, ; Xu, Wu, Yin, Xue, & Gou, ). REACTOME (http://www.reactome.org/), Kyoto Encyclopedia of Genes and Genomes (KEGG) (http://www.genome.jp/kegg/pathway.html), and BIOCARTA (https://cgap.nci.nih.gov/Pathways/BioCarta_Pathways) pathway databases were used to perform pathway analyses among survival‐related mRNAs screened by univariate Cox analysis.…”

Section: Methodsmentioning

confidence: 99%

Identification of a five‐mRNA signature as a novel potential prognostic biomarker in pediatric Wilms tumor

Lin

Chen

et al. 2019

Molec Gen & Gen Med

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Background: The aim of this study was to generate a prognostic model to predict survival outcome in pediatric Wilms tumor (WT). Methods: The data including mRNA expression and clinical information of pediatric WT patients were downloaded from the Therapeutically Available Research to Generate Effective Treatments (TARGET) database. The differentially expressed genes were identified and a prognostic signature of pediatric WT was generated according to the results of univariate and multivariate Cox analysis. Receiver operating characteristic (ROC) curve was used to evaluate the five-mRNA signature in pediatric Wilms tumor patients. Bootstrap test with 500 times was used to perform the internal validation. Results: We identified 6,964 differentially expressed mRNAs associated with pediatric WT, including 3,190 downregulated mRNAs and 3,774 up-regulated mRNAs. Univariate and multivariate Cox analysis identified five mRNAs (SPRY1, SPIN4, MAP7D3, C10orf71, and SPAG11A) to establish a predictive model. The risk score formula is as follows: Risk score = 0.3036*SPIN4 + 0.8576*MAP7D3 −0.1548*C10orf71 −0.7335*SPRY1 −0.2654*SPAG11A. The pediatric WT patients were divided into lowrisk group and high-risk group based on the median risk score (value = 1.1503). The receiver operating characteristic (ROC) curve analysis revealed good performance of the 5-mRNA prognostic model (the area under the curve [AUC] was 0.821). Bootstraptest (Bootstrap resampling times = 500) was used to perform the internal validation and revealed that the AUC was 0.822. REACTOME, KEGG, and BIOCARTA pathway analyses demonstrated that these survival-related genes were mainly enriched in ErbB2 and ErbB3 signaling pathways, and calcium signaling pathway. Conclusion: The five-mRNA signature can predict the prognosis of patients with pediatric WT. It has significant implication in the understanding of therapeutic targets for pediatric WT patients. However, further study is needed to validate this five-mRNA signature and uncover more novel diagnostic or prognostic mRNAs candidates in pediatric WT patients.

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“…The Cytoscape version 3.7.2 was used to constructed networks, which is a java based open source software (Demchak et al, 2014). Functional pathways of resveratrol related to NDs were analyzed using GO enrichment and KEGG pathways analysis based upon the database for Annotation, Visualization and Integrated Discovery (DAVID) version 6.8 (https://david.ncifcrf.gov/) (Ke et al, 2019). P < 0.05 suggested the enrichment degree had statistically significant and the pathway results might be essential functional mechanisms of resveratrol in the treatment of NDs.…”

Section: Go Function Enrichment and Kegg Pathway Analysismentioning

confidence: 99%

Resveratrol: Multi-Targets Mechanism on Neurodegenerative Diseases Based on Network Pharmacology

Wang

Liu

et al. 2020

Front. Pharmacol.

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Resveratrol is a natural polyphenol in lots of foods and traditional Chinese medicines, which has shown promising treatment for neurodegenerative diseases (NDs). However, the molecular mechanisms of its action have not been systematically studied yet. In order to elucidate the network pharmacological prospective effects of resveratrol on NDs, we assessed of pharmacokinetics (PK) properties of resveratrol, studied target prediction and network analysis, and discussed interacting pathways using a network pharmacology method. Main PK properties of resveratrol were acquired. A total of 13,612 genes related to NDs, and 138 overlapping genes were determined through matching the 175 potential targets of resveratrol with disease-associated genes. Gene Ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed to obtain more in-depth understanding of resveratrol on NDs. Accordingly, nodes with high degrees were obtained according using a PPI network, and AKT1, TP53, IL6, CASP3, VEGFA, TNF, MYC, MAPK3, MAPK8, and ALB were identified as hub target genes, which showed better affinity with resveratrol in silico studies. In addition, our experimental results demonstrated that resveratrol markedly enhanced the decreased levels of Bcl-2 and significantly reduced the increased expression of Bax and Caspase-3 in hippocampal neurons induced by glutamate exposure. Western blot results confirmed that resveratrol inhibited glutamate-induced apoptosis of hippocampal neurons partly by regulating the PI3K/AKT/mTOR pathway. In conclusion, we found that resveratrol could target multiple pathways forming a systematic network with pharmacological effects.

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Identification of key genes and pathways in benign prostatic hyperplasia

Cited by 33 publications

References 31 publications

Development and validation of a molecular prognostic index of bladder cancer based on immunogenomic landscape analysis

Development and validation of a molecular prognostic index of bladder cancer based on immunogenomic landscape analysis

Identification of a five‐mRNA signature as a novel potential prognostic biomarker in pediatric Wilms tumor

Resveratrol: Multi-Targets Mechanism on Neurodegenerative Diseases Based on Network Pharmacology

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