Where does degarelix fit into prostate cancer therapy in comparison to leuprolide (Eligard, Lupron)? When would you choose one product over the other?

Comment by InpharmD Researcher

The gene microarray data related to PM were downloaded from the Gene Expression Omnibus database. The analyses using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes, gene set enrichment analysis (GSEA), and protein-protein interaction (PPI) networks were performed on differentially expressed genes (DEGs). The hub genes of PM were identified using weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) algorithm, and the diagnostic accuracy of hub markers for PM was assessed using the receiver operating characteristic curve. In addition, the level of infiltration of 28 immune cells in PM and their interrelationship with hub genes were analyzed using single-sample GSEA. In the U.S., a push for revisions of the FD&C Act emerged from Congressional hearings led by Senator Estes Kefauver of Tennessee in 1959. The hearings covered a wide range of policy issues, including advertising abuses, questionable efficacy of drugs, and the need for greater regulation of the industry. While momentum for new legislation temporarily flagged under extended debate, a new tragedy emerged that underscored the need for more comprehensive regulation and provided the driving force for the passage of new laws.

Background

A total of 420 DEGs were identified. The biological functions and signaling pathways closely associated with PM were inflammatory and immune processes. A series of four expression modules were obtained by WGCNA analysis, with the turquoise module having the highest correlation with PM; 196 crossover genes were obtained by combining DEGs. Subsequently, six hub genes were finally identified as the potential biomarkers of PM using LASSO algorithm and validation set verification analysis. In the immune cell infiltration analysis, the infiltration of T lymphocytes and subpopulations, dendritic cells, macrophages, and natural killer cells was more significant in the PM.

Polymyositis (PM) is an acquirable muscle disease with proximal muscle involvement of the extremities as the main manifestation; it is a category of idiopathic inflammatory myopathy. This study aimed to identify the key biomarkers of PM, while elucidating PM-associated immune cell infiltration and immune-related pathways. A series of four expression modules were obtained by WGCNA analysis, with the turquoise module having the highest correlation with PM; 196 crossover genes were obtained by combining DEGs. Subsequently, six hub genes were finally identified as the potential biomarkers of PM using LASSO algorithm and validation set verification analysis.

A weighted gene coexpression network was constructed, and the genes were divided into 66 modules. The enriched functions and candidate pathway modules included interferon-γ, type I interferon, cellular response to interferon-γ, neutrophil activation, neutrophil degranulation, neutrophil-mediated immunity and neutrophil activation involved in the immune response. A total of 22 hub genes were identified. The Mann-Whitney U test was performed on these 22 genes using the three datasets of muscle samples and one dataset of whole blood samples, and two genes significantly differentially expressed in all datasets were obtained: VCAM1 and LY96. Receiver operating characteristic curve analysis determined that VCAM1 and LY96 gene expression can distinguish PM from healthy controls (the area under the curve [AUC] was greater than 0.75). Logistic regression analysis was performed on the combination of LY96 and VCAM1. The accuracy, sensitivity, specificity, and AUC of the combination reached 1.0. GSEA of VCAM1 and LY96 revealed their relation to 'inflammatory response', 'TNF-α signalling via NF-κB', 'complement' and 'myogenesis'. CMap research revealed a few compounds with the potential to counteract the effects of the dysregulated molecular signature in PM.

To identify the candidate genes of PM, microarray datasets GSE128470, GSE3112, GSE39454 and GSE125977 were obtained from the Gene Expression Omnibus database. The gene network of GSE128470 was constructed, and WGCNA was used to divide genes into different modules. Subsequently, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were applied to the most PM-related modules. The datasets were used to verify the expression profile and diagnostic capabilities of the hub genes. Additionally, gene set enrichment analysis (GSEA) was carried out. Moreover, gene signatures were then used as a search query to explore the connectivity map (CMap).

Relevant Prescribing Information

We used WGCNA to observe all aspects of PM, which helped to elucidate the molecular mechanisms of PM onset and progression and provide candidate targets for the diagnosis and treatment of PM. Key Points • Four microarray datasets were analysed in patients with polymyositis and healthy controls, and VCAM1 and LY96 were significant genes in all datasets. • GSEA of VCAM1 and LY96 revealed that they were mainly related to 'inflammatory response', 'TNF-α signalling via NF-κB', 'complement' and 'myogenesis'. • CMap found a few compounds such as dimethyloxalylglycine and HNMPA-(AM)3 with the potential to counteract the effects of the dysregulated molecular signature in PM. The purpose of our present study was to, for the first time, identify key genes associated with postpartum depression (PPD) and discovery the potential molecular mechanisms of this condition. Methods: First, microarray expression profiles GSE45603 dataset were acquired from the Gene Expression Omnibus (GEO) in National Center for Biotechnology Information (NCBI). The weighted gene co-expression network analysis (WGCNA) was performed to identify the top three modules from differentially expressed genes (DEGs). Furthermore, cross-validated differential gene expression analysis of the top three modules and DEGs was used to identify the hub genes. Gene set enrichment analysis (GSEA) was conducted to identify the potential functions of the hub genes. We conducted a Receiver Operator Characteristic (ROC) curve to verify the diagnostic efficiencies of the hub genes. Lastly, GSE44132 dataset was used to search the association between the methylation profiles of the hub genes and susceptibility to PPD.

Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

Where does degarelix fit into prostate cancer therapy in comparison to leuprolide (Eligard, Lupron)? When would you choose one product over the other?

Level of evidence

B - One high-quality study or multiple studies with limitations  Read more→


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Design

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Study Groups

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White

      

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InpharmD Researcher Critique

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