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Objective: The purpose of this study was to identify potential biomarkers in the tubulointerstitium of focal segmental glomerulosclerosis (FSGS) and comprehensively analyze its mRNA-miRNA-lncRNA/circRNA network. Methods: The expression data (GSE108112 and GSE200818) were downloaded from the Gene Expression Omnibus database (https://www.ncbi.nlm.nih.gov/geo/). Identification and enrichment analysis of differentially expressed genes (DEGs) were performed. the PPI networks of the DEGs were constructed and classified using the Cytoscape molecular complex detection (MCODE) plugin. Weighted gene coexpression network analysis (WGCNA) was used to identify critical gene modules. Least absolute shrinkage and selection operator regression analysis were used to screen for key biomarkers of the tubulointerstitium in FSGS, and the receiver operating characteristic curve was used to determine their diagnostic accuracy. The screening results were verified by quantitative real-time-PCR (qRT-PCR) and Western blot. The transcription factors (TFs) affecting the hub genes were identified by Cytoscape iRegulon. The mRNA-miRNA-lncRNA/circRNA network for identifying potential biomarkers was based on the starBase database. Results: A total of 535 DEGs were identified. MCODE obtained eight modules. The green module of WGCNA had the greatest association with the tubulointerstitium in FSGS. PPARG coactivator 1 alpha (PPARGC1A) was screened as a potential tubulointerstitial biomarker for FSGS and verified by qRT-PCR and Western blot. The TFs FOXO4 and FOXO1 had a regulatory effect on PPARGC1A. The ceRNA network yielded 17 miRNAs, 32 lncRNAs, and 50 circRNAs. Conclusions: PPARGC1A may be a potential biomarker in the tubulointerstitium of FSGS. The ceRNA network contributes to the comprehensive elucidation of the mechanisms of tubulointerstitial lesions in FSGS. [ABSTRACT FROM AUTHOR]

The aim of our study was to identify key biomarkers of glomeruli in focal glomerulosclerosis (FSGS) and analyze their relationship with the infiltration of immune cells. The expression profiles (GSE108109 and GSE200828) were obtained from the GEO database. The differentially expressed genes (DEGs) were filtered and analyzed by gene set enrichment analysis (GSEA). MCODE module was constructed. Weighted gene coexpression network analysis (WGCNA) was performed to obtain the core gene modules. Least absolute shrinkage and selection operator (LASSO) regression was applied to identify key genes. ROC curves were employed to explore their diagnostic accuracy. Transcription factor prediction of the key biomarkers was performed using the Cytoscape plugin IRegulon. The analysis of the infiltration of 28 immune cells and their correlation with the key biomarkers were performed. A total of 1474 DEGs were identified. Their functions were mostly related to immune-related diseases and signaling pathways. MCODE identified five modules. The turquoise module of WGCNA had significant relevance to the glomerulus in FSGS. TGFB1 and NOTCH1 were identified as potential key glomerular biomarkers in FSGS. Eighteen transcription factors were obtained from the two hub genes. Immune infiltration showed significant correlations with T cells. The results of immune cell infiltration and their relationship with key biomarkers implied that NOTCH1 and TGFB1 were enhanced in immune-related pathways. TGFB1 and NOTCH1 may be strongly correlated with the pathogenesis of the glomerulus in FSGS and are new candidate key biomarkers. T-cell infiltration plays an essential role in the FSGS lesion process. [ABSTRACT FROM AUTHOR]

While the prognosis of multiple myeloma (MM) has significantly improved over the last decade because of new treatment options, it remains incurable. Aetiological explanations and biological targets based on genomics may provide additional help for rational disease intervention. Three microarray datasets associated with MM were downloaded from the Gene Expression Omnibus (GEO) database. GSE125364 and GSE39754 were used as the training set, and GSE13591 was used as the verification set. The differentially expressed genes (DEGs) were obtained from the training set, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to annotate their functions. The hub genes were derived from the combined results of a protein–protein interaction (PPI) network and weighted gene coexpression network analysis (WGCNA). The receiver operating characteristic (ROC) curves of hub genes were plotted to evaluate their clinical diagnostic value. Biological processes and signaling pathways associated with hub genes were explained by gene set enrichment analysis (GSEA). A total of 1759 DEGs were identified. GO and KEGG pathway analyses suggested that the DEGs were related to the process of protein metabolism. RPN1, SEC61A1, SPCS1, SRPR, SRPRB, SSR1 and TRAM1 were proven to have clinical diagnostic value for MM. The GSEA results suggested that the hub genes were widely involved in the N-glycan biosynthesis pathway. The hub genes identified in this study can partially explain the potential molecular mechanisms of MM and serve as candidate biomarkers for disease diagnosis. [ABSTRACT FROM AUTHOR]

Aim: To investigate whether long non-coding RNAs (lncRNAs) can be utilized as molecular biomarkers in predicting the occurrence and progression of chromophobe renal cell carcinoma. Methods & results: Genetic and related clinical traits of chromophobe renal cell carcinoma were downloaded from the Cancer Genome Atlas and used to construct modules using weighted gene coexpression network analysis. In total, 44,889 genes were allocated into 21 coexpression modules depending on intergenic correlation. Among them, the green module was the most significant key module identified by module–trait correlation calculations (R2 = 0.43 and p = 4e-04). Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses demonstrated that genes in the green module were enriched in many pathways. Coexpression, protein–protein interaction networks, screening for differentially expressed genes, and survival analysis were used to select hub lncRNAs. Five hub lncRNAs (TTK, CENPE, KIF2C, BUB1, and RAD51AP1) were selected out. Conclusion: Our findings suggest that the five lncRNAs may act as potential biomarkers for chromophobe renal cell carcinoma progression and prognosis. [ABSTRACT FROM AUTHOR]

Acute myeloid leukaemia (AML) is a common blood cancer with rapid progression and a high death rate. The aim of this study was to illustrate the molecular mechanism and identify potential prognostic genes by performing weighted gene coexpression network analysis (WGCNA) of AML. WGCNA of AML was performed with R software based on GDC The Cancer Genome Atlas (TCGA) Acute Myeloid Leukaemia (LAML) RNA-seq data from TCGA database. The gene modules showing significant correlation with the M0-M7 subtypes and the NPMc mutation were analysed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Hub genes from the key modules were identified using the cytoHubba package, and the prognostic values of these hub genes were analysed with a Cox proportional hazards model based on TCGA clinical data. A total of 151 patients from the TCGA database with RNA-seq data were included in the present study. The weighted gene coexpression network contained 21 coexpression modules. Three modules (blue, yellow and purple) were highly correlated with AML subtypes and the NPMc mutation. In total, six key hub genes were identified from the AML subtype- and NPMc mutation-related modules: TLR8, SLC15A3, ADAP2, HOXA6 and HOXA10. Kaplan–Meier curve analysis showed that the five hub genes in the gene expression network are significantly associated with AML prognosis. WGCNA of AML performed in the present study revealed potential prognostic genes that not only have important clinical significance for prognosis but also provide important clues for identifying effective targets in AML therapeutic strategies. [ABSTRACT FROM AUTHOR]