Aim:Until now, identification of drug targets for treatment of patients with specific stages of colorectal cancer (CRC) has remained a challenging field of research. Herein, we aimed to identify the key genes and regulatory networks involved in each stage of CRC.Results:The results of gene expression profiles were integrated with protein–protein interaction networks, and topologically analyzed. The most important regulatory genes (e.g., CDK1, UBC, ESR1 and ATXN1) and signaling pathways (e.g., Wnt, MAPK and JAK-STAT) in CRC initiation, progression and metastasis were identified. In vitro analysis confirmed some in silico findings.Conclusion:Our study introduces functional hub genes, subnetworks, prioritizes signaling pathways and novel biomarkers in CRC that may guide further development of targeted therapy programs.
Epstein-Barr virus (EBV) is the most common cause of infectious mononucleosis (IM) and establishes lifetime infection associated with a variety of cancers and autoimmune diseases. The aim of this study was to develop an integrative gene regulatory network (GRN) approach and overlying gene expression data to identify the representative subnetworks for IM and EBV latent infection (LI). After identifying differentially expressed genes (DEGs) in both IM and LI gene expression profiles, functional annotations were applied using gene ontology (GO) and BiNGO tools, and construction of GRNs, topological analysis and identification of modules were carried out using several plugins of Cytoscape. In parallel, a human-EBV GRN was generated using the Hu-Vir database for further analyses. Our analysis revealed that the majority of DEGs in both IM and LI were involved in cell-cycle and DNA repair processes. However, these genes showed a significant negative correlation in the IM and LI states. Furthermore, cyclin-dependent kinase 2 (CDK2) - a hub gene with the highest centrality score - appeared to be the key player in cell cycle regulation in IM disease. The most significant functional modules in the IM and LI states were involved in the regulation of the cell cycle and apoptosis, respectively. Human-EBV network analysis revealed several direct targets of EBV proteins during IM disease. Our study provides an important first report on the response to IM/LI EBV infection in humans. An important aspect of our data was the upregulation of genes associated with cell cycle progression and proliferation.
Most of the current cancer treatment approaches are invasive along with a broad spectrum of side effects. Furthermore, cancer drug resistance known as chemoresistance is a huge obstacle during treatment. This study aims to predict the resistance of several cancer cell-lines to a drug known as Cisplatin. In this papers the NCBI GEO database was used to obtain data and then the harvested data was normalized and its batch effects were corrected by the Combat software. In order to select the appropriate features for machine learning, the feature selection/reduction was performed based on the Fisher Score method. Six different algorithms were then used as machine learning algorithms to detect Cisplatin resistant and sensitive samples in cancer cell lines. Moreover, Differentially Expressed Genes (DEGs) between all the sensitive and resistance samples were harvested. The selected genes were enriched in biological pathways by the enrichr database. Topological analysis was then performed on the constructed networks using Cytoscape software. Finally, the biological description of the output genes from the performed analyses was investigated through literature review. Among the six classifiers which were trained to distinguish between cisplatin resistance samples and the sensitive ones, the KNN and the Naïve Bayes algorithms were proposed as the most convenient machines according to some calculated measures. Furthermore, the results of the systems biology analysis determined several potential chemoresistance genes among which PTGER3, YWHAH, CTNNB1, ANKRD50, EDNRB, ACSL6, IFNG and, CTNNB1 are topologically more important than others. These predictions pave the way for further experimental researches.
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