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. 2024 Jul;14(7):1166-1191.
doi: 10.1002/2211-5463.13807. Epub 2024 May 23.

Exploring gene regulatory interaction networks and predicting therapeutic molecules for hypopharyngeal cancer and EGFR-mutated lung adenocarcinoma

Affiliations

Exploring gene regulatory interaction networks and predicting therapeutic molecules for hypopharyngeal cancer and EGFR-mutated lung adenocarcinoma

Abanti Bhattacharjya et al. FEBS Open Bio. 2024 Jul.

Abstract

Hypopharyngeal cancer is a disease that is associated with EGFR-mutated lung adenocarcinoma. Here we utilized a bioinformatics approach to identify genetic commonalities between these two diseases. To this end, we examined microarray datasets from GEO (Gene Expression Omnibus) to identify differentially expressed genes, common genes, and hub genes between the selected two diseases. Our analyses identified potential therapeutic molecules for the selected diseases based on 10 hub genes with the highest interactions according to the degree topology method and the maximum clique centrality (MCC). These therapeutic molecules may have the potential for simultaneous treatment of these diseases.

Keywords: EGFR‐mutated lung adenocarcinoma; Gene Expression Omnibus; degree topology, therapeutic molecule; hub gene; hypopharyngeal cancer.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Fig. 1
Fig. 1
Diagram representing the proposed methodology of the current research. For hypopharyngeal cancer and EGFR‐mutated lung adenocarcinoma, two datasets are used. Each dataset has eight samples. Using the R programming language, the DEGs (differentially expressed genes) from those two datasets are retrieved. The VENNY tool is used to find out the common genes between these two diseases. With the aid of these widespread DEGs, GO terms, pathways, PPI networks, TF‐miRNA, and hub genes are identified. Functional association, TF‐gene, gene‐miRNA, gene–disease, and some therapeutic compounds are anticipated based on the hub genes of individuals with hypopharyngeal cancer and EGFR‐mutated lung adenocarcinoma who have these two diseases concurrently.
Fig. 2
Fig. 2
Venn diagram of shared DEGs. Thirty‐two common genes were found between HC and EGFR‐mutated LC. Common DEGs were 2% among 1667 DEGs.
Fig. 3
Fig. 3
Top 10 GO terms concomitant to biological process, molecular function, and cellular component pinpointing entrenched on the combined score (the log of the P‐value from Fisher's exact test and multiplying that by the z‐score of the deviation from the expected rank).
Fig. 4
Fig. 4
Top 10 pathways from (A) Reactome, (B) KEGG, (C) WikiPathways, and (D) BioCarta pinpointing entrenched on the combined score (the log of the P‐value from Fisher's exact test and multiplying that by the z‐score of the deviation from the expected rank).
Fig. 5
Fig. 5
Visualization of TF‐miRNA coregulatory network through NetworkAnalyst. Green‐black highlighted nodes indicate seeds, red diamond‐shaped nodes for TF, and blue box‐shaped nodes for miRNA.
Fig. 6
Fig. 6
Protein–protein interaction network through string.
Fig. 7
Fig. 7
PPIs network through cytoscape using the directly interconnected genes.
Fig. 8
Fig. 8
PPIs network obtained through IMeX intercome of InnateDB database contains 972 nodes, 1110 edges, and 16 seeds.
Fig. 9
Fig. 9
The top 10 hub genes network according to the degree topology method through cytoscape.
Fig. 10
Fig. 10
The top 10 hub genes network accordance with the maximal clique centrality (MCC) method through cytoscape.
Fig. 11
Fig. 11
Functional association network through genemania. 36.76% coexpression, 31.14% physical interactions, 15.88% predicted, 6.48% pathway, 4.72% colocalization, 4.51% shared protein domains and 0.50% genetic interactions are found here.
Fig. 12
Fig. 12
Visualization of TF‐gene association network through networkanalyst. Red diamond‐shaped nodes indicate TF‐gene and green‐black highlighted circle‐shaped nodes for seeds.
Fig. 13
Fig. 13
Visualization of gene‐miRNA network through networkanalyst. Green‐black highlighted nodes indicate 17 seeds and blue box‐shaped nodes for miRNA, edges connect the genes and miRNAs.
Fig. 14
Fig. 14
Gene–disease network is divided into three subnetworks. Subnetwork1 represents genes (HLA‐B, DUSP5, ARHGDIB, JUN, HBEGF) and their corresponding associated diseases, Subnetwork2 acts for HLA‐DRA genes with its associated diseases and Subnetwork3 focuses on the MUC4 gene with its correspondent genes. Here, green‐black highlighted nodes for seeds and red box‐shaped nodes for associated diseases.

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