A network-biology approach for identification of key genes and pathways involved in malignant peritoneal mesothelioma

Mahfuz, A M U B; Zubair-Bin-Mahfuj, A. M.; Podder, Dibya Joti

doi:10.5808/gi.21019

Cited by 7 publications

(7 citation statements)

References 54 publications

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“…Previous studies have indicated that TFs and miRNAs can either induce or suppress the expression of their target genes [25,26]. e binding of miRNA to the promoter can induce the expression of the target gene while binding to 3′ UTR and 5′ UTR, as well as the coding sequence can result in gene silencing [26,27]. e present study built a GRN consisting of the hub genes, miRNAs, and TFs.…”

Section: Grn Constructionmentioning

confidence: 92%

“…us, inhibition of protein kinases has become a promising strategy in cancer therapy, which has already provided satisfying effects [34]. e online Kinase Enrichment Analysis 2 (KEA2) web tool, which is available at https://www.maayanlab.net/KEA2/ [35], was employed to identify protein kinase(s) affecting TFs regulating the hub genes [27]. e KEA2 is being made by the Ma'ayan Lab at the Icahn School of Medicine at Mount Sinai, New York, by manually curating interactions between kinases and their targets in the literature.…”

Section: Grn Constructionmentioning

confidence: 99%

“…Following the methods of Mahfuz et al [27], the online DrugBank database (version 5.1.8, released on 2020-01-03; available at https://go.drugbank.com/) [36] was used to identify experimental/investigational approved drugs for inhibiting and activating the proteins encoded by the upregulated and downregulated hub genes in ameloblastoma, respectively. is may accelerate the development of new therapies for ameloblastoma in the future.…”

Section: Identification Of Approved Drugs Acting On Hub Proteinsmentioning

confidence: 99%

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Potential Biomarkers and Signaling Pathways Associated with the Pathogenesis of Primary Ameloblastoma: A Systems Biology Approach

Bayat

Mirzaeian

Taherkhani

2022

International Journal of Dentistry

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Objective. Ameloblastoma is a benign odontogenic tumor that may lead to ameloblastic carcinoma. is study aimed to determine potential signaling pathways and biological processes, critical genes and their regulating transcription factors (TFs), and miRNAs, as well as protein kinases involved in the etiology of primary ameloblastoma. Methods. e dataset GSE132472 was obtained from the GEO database, and multivariate statistical analyses were applied to identify di erentially expressed genes (DEGs) in primary ameloblastoma tissues compared to the corresponding normal gingiva samples. A protein-protein interaction (PPI) map was built using the STRING database. e Cytoscape software identi ed signi cant modules and the hub genes within the PPI network. Gene Ontology annotation and signaling pathway analyses were executed by employing the DAVID and Reactome databases, respectively. Signi cant TFs and miRNAs acting on the hub genes were identi ed using the iRegulon plugin and MiRWalk 2.0 database, respectively. A protein kinase enrichment analysis was conducted using the online Kinase Enrichment Analysis 2 (KEA2) web server. e approved drugs acting on the hub genes were also found. Results. A total of 1,629 genes were di erentially expressed in primary ameloblastoma (P value <0.01 and |Log2FC| > 1). HRAS, CDK1, MAPK3, ERBB2, COL1A1, CYCS, and BRCA1 demonstrated high degree and betweenness centralities in the PPI network. E2F4 was the most signi cant TF acting on the hub genes. BTK was the protein kinase signi cantly enriched by the TFs. Cholesterol biosynthesis was considerably involved in primary ameloblastoma. Conclusions. is study provides an intuition into the potential mechanisms involved in the etiology of ameloblastoma.

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Section: Grn Constructionmentioning

confidence: 92%

Section: Grn Constructionmentioning

confidence: 99%

Section: Identification Of Approved Drugs Acting On Hub Proteinsmentioning

confidence: 99%

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Potential Biomarkers and Signaling Pathways Associated with the Pathogenesis of Primary Ameloblastoma: A Systems Biology Approach

Bayat

Mirzaeian

Taherkhani

2022

International Journal of Dentistry

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“…In this regard, miRNAs could enhance their target genes' expression if they bind to the promoter region. However, these small molecules could result in gene silencing if they attach to other parts of the genes, such as 3′ untranslated region (UTR), 5′ UTR, and the coding sequence [ 50 , 51 ]. MiRNAs contribute to gene regulation and play a decisive role in several biological procedures, such as cellular proliferation and differentiation, apoptosis, development, inflammation, carcinogenesis, and metastasis.…”

Section: Introductionmentioning

confidence: 99%

Prognostic biomarkers and molecular pathways mediating Helicobacter pylori–induced gastric cancer: a network-biology approach

2023

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Cancer of the stomach is the second most frequent cancer-related death worldwide. The survival rate of patients with gastric cancer (GC) remains fragile. There is a requirement to discover biomarkers for prognosis approaches. Helicobacter pylori in the stomach is closely associated with the progression of GC. We identified the genes associated with poor/favorable prognosis in H. pylori–induced GC. Multivariate statistical analysis was applied on the Gene Expression Omnibus (GEO) dataset GSE54397 to identify differentially expressed miRNAs (DEMs) in gastric tissues with H. pylori–induced cancer compared with the H. pylori–positive with non-cancerous tissue. A protein interaction map (PIM) was built and subjected to DEMs targets. The enriched pathways and biological processes within the PIM were identified based on substantial clusters. Thereafter, the most critical genes in the PIM were illustrated, and their prognostic impact in GC was investigated. Considering p-value less than 0.01 and |Log2 fold change| as >1, five microRNAs demonstrated significant changes among the two groups. Gene functional analysis revealed that the ubiquitination system, neddylation pathway, and ciliary process are primarily involved in H. pylori–induced GC. Survival analysis illustrated that the overexpression of DOCK4, GNAS, CTGF, TGF-b1, ESR1, SELE, TIMP3, SMARCE1, and TXNIP was associated with poor prognosis, while increased MRPS5 expression was related to a favorable prognosis in GC patients. DOCK4, GNAS, CTGF, TGF-b1, ESR1, SELE, TIMP3, SMARCE1, TXNIP, and MRPS5 may be considered prognostic biomarkers for H. pylori–induced GC. However, experimental validation is necessary in the future.

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“…Mesothelioma appears to be characterized by chromosome rearrangements and gene mutations/deletions ( 16 ). More recently, the molecular landscape of mesothelioma has been enriched by the discovery of susceptibility familial factors that influence the impact of asbestos, target mutations in oncogenes and tumour suppressor genes, and epigenetic changes ( 17 , 18 ).…”

Section: Introductionmentioning

confidence: 99%

Molecular Pathways in Peritoneal Mesothelioma: A Minireview of New Insights

et al. 2022

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Mesothelioma is a rare malignant neoplasm with poor survival. It mainly affects the pleura (90%) but can arise in all serous cavities: peritoneum (5-10%), pericardium and tunica vaginalis testis (<1%). The onset of pleural mesothelioma is strictly related to asbestos exposure with a long latency time. The causal link with asbestos has also been suggested for peritoneal mesothelioma, while the importance of exposure in the onset of pericardial and tunica vaginalis testis mesotheliomas is not well known. Mesothelioma remains an aggressive and fatal disease with a five-year mortality rate higher than 95%. However, new therapeutic approaches based on molecular-targeted and immunomodulatory therapies are being explored but have conflicting results. In this context, the identification of critical targets appears mandatory. Awareness of the molecular and physiological changes leading to the neoplastic degeneration of mesothelial cells and the identification of gene mutations, epigenetic alterations, gene expression profiles and altered pathways could be helpful for selecting targetable mechanisms and molecules. In this review, we aimed to report recent research in the last 20 years focusing on the molecular pathways and prognostic factors in peritoneal mesothelioma and their possible diagnostic and therapeutic implications.

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A network-biology approach for identification of key genes and pathways involved in malignant peritoneal mesothelioma

Cited by 7 publications

References 54 publications

Potential Biomarkers and Signaling Pathways Associated with the Pathogenesis of Primary Ameloblastoma: A Systems Biology Approach

Potential Biomarkers and Signaling Pathways Associated with the Pathogenesis of Primary Ameloblastoma: A Systems Biology Approach

Prognostic biomarkers and molecular pathways mediating Helicobacter pylori–induced gastric cancer: a network-biology approach

Molecular Pathways in Peritoneal Mesothelioma: A Minireview of New Insights

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