Identification of Key Modules, Hub Genes, and Noncoding RNAs in Chronic Rhinosinusitis with Nasal Polyps by Weighted Gene Coexpression Network Analysis
BIOMED RESEARCH INTERNATIONAL
Authors: Zhou, Xuanchen; Zhen, Xiaoyue; Liu, Yiqing; Cui, Zhaoyang; Yue, Zhiyong; Xu, Anting; Han, Jie
Abstract
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease with relatively easy recurrence. However, the precise molecular mechanisms of this disease are poorly known. Based on gene sequencing data obtained from the Gene Expression Omnibus (GEO) database, we constructed coexpression networks by weighted gene coexpression network analysis (WGCNA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by the Database for Annotation, Visualization, and Integrated Discovery (DAVID). The core gene of pathogenesis, CRSwNP, was screened by protein-protein interaction data (PPI) from the HPRD database. Unsupervised clustering was applied to screen hub genes related to the phenotype of CRSwNP. Blue and turquoise modules were found to be most significantly related to the pathogenicity of CRSwNP. Functional enrichment analysis showed that cell proliferation in the blue modules, the apoptotic process in the turquoise module, and the cancer pathway in both modules were mostly significantly correlated with the development of CRSwNP. The noncoding RNAs (long noncoding RNA and microRNA) and the top 10 core genes in each module were found to be associated with the pathogenesis of CRSwNP. A total of nine hub genes were identified to be related to the CRSwNP phenotype. By qRT-PCR analysis, AKT1, CDH1, PIK3R1, CBL, LRP1, MALAT1, and XIST were proven to be associated with the pathogenesis of CRSwNP. AGR2, FAM3D, PIP, DSE, and TMC were identified to be related to the CRSwNP phenotype. Further exploration of these genes will reveal more important information about the mechanisms of CRSwNP.
Comparative proteomic network signatures in seminal plasma of infertile men as a function of reactive oxygen species
CLINICAL PROTEOMICS
Authors: Agarwal, Ashok; Ayaz, Ahmet; Samantal', Luna; Sharma, Rakesh; Assidi', Mourad; Abuzenadah, Adel M.; Sabanegh, Edmund
Abstract
Background: Reactive oxygen species (ROS) plays a major role in the pathology of male infertility. It is an independent biomarker of sperm function. Seminal plasma is a natural reservoir of antioxidants responsible for the nourishment, protection, capacitation, and motility of sperm within the female reproductive tract resulting in successful fertilization and implantation of the embryo. A comparative proteomic analysis of seminal plasma proteins from fertile men and infertile men with varying levels of ROS was carried out to identify signature proteins involved in ROS-mediated reproductive dysfunction. Methods: A total of 42 infertile men presenting with infertility and 17 proven fertile donors were enrolled in the study. ROS levels were measured in the seminal ejaculates by chemiluminescence assay. Infertile men were subdivided into Low ROS (0 <93 RLU/s/106 sperm; n = 11), Medium ROS (>93-500 RLU/s/106 sperm; n = 17) and High ROS (>500 RLU/s/106 sperm; n = 14) groups and compared with fertile men (4-50 RLU/s/106 sperm). 4 subjects from fertile group and 4 each from the Low, Medium and High ROS were pooled. 1D gel electrophoresis followed by in -gel digestion and LC/MS MS in a LTQ-Orbitrap Elite hybrid mass spectrometer system was used for proteome analysis. Identification of differentially expressed proteins (DEPs), their cellular localization and involvement in different pathways were examined utilizing bioinformatics tools. Results: The results indicate that proteins involved in biomolecule metabolism, protein folding and protein degradation are differentially modulated in all three infertile patient groups in comparison to fertile controls. Membrane metallo-endopeptidase (MME) was uniformly overexpressed (>2 fold) in all infertile groups. Pathway involving 35 focus proteins in post -translational modification of proteins, protein folding (heat shock proteins, molecular chaperones) and developmental disorder was overexpressed in the High ROS group compared with fertile control group. MME was one of the key proteins in the pathway. FAM3D was uniquely expressed in fertile group. Conclusion: We have for the first time demonstrated the presence of 35 DEPs of a single pathway that may lead to impairment of sperm function in men with Low, Medium or High ROS levels by altering protein turn over. MME and FAM3D along with ROS levels in the seminal plasma may serve as good markers for diagnosis of male infertility.