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. 2024 Dec 6:11:1502509.
doi: 10.3389/fmolb.2024.1502509. eCollection 2024.

Identification of genetic associations between acute myocardial infarction and non-small cell lung cancer

Hao Zheng #  1 , Jie Wang #  2   3 , Yijia Zheng  1 , Xiaofan Hong  1 , Luxi Wang  4
Affiliations

Identification of genetic associations between acute myocardial infarction and non-small cell lung cancer

Hao Zheng et al. Front Mol Biosci. .

Abstract

Introduction: A growing body of evidence suggests a potential connection between myocardial infarction (MI) and lung cancer (LC). However, the underlying pathogenesis and molecular mechanisms remain unclear. This research aims to identify common genes and pathways between MI and LC through bioinformatics analysis.

Methods: Two public datasets (GSE166780 and GSE8569) were analyzed to identify differentially expressed genes (DEGs). Common DEGs were enriched using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Hub genes were identified and their diagnostic performance was evaluated. Gene co-expression networks, as well as regulatory networks involving miRNA-hub genes and TF-hub genes, were also constructed. Finally, candidate drugs were predicted.

Results: Among the datasets, 34 common trend DEGs were identified. Enrichment analysis linked these DEGs to key biological processes, cellular components, and molecular functions. Eight hub genes (CEBPA, TGFBR2, EZH2, JUNB, JUN, FOS, PLAU, COL1A1) were identified, demonstrating promising diagnostic accuracy. Key transcription factors associated with these hub genes include SP1, ESR1, CREB1, ETS1, NFKB1, and RELA, while key miRNAs include hsa-mir-101-3p, hsa-mir-124-3p, hsa-mir-29c-3p, hsa-mir-93-5p, and hsa-mir-155-5p. Additionally, potential therapeutic drugs were identified, with zoledronic acid anhydrous showing potential value in reducing the co-occurrence of the two diseases.

Discussion: This study identified eight common signature genes shared between NSCLC and AMI. Validation datasets confirmed the diagnostic value of key hub genes COL1A1 and PLAU. These findings suggest that shared hub genes may serve as novel therapeutic targets for patients with both diseases. Ten candidate drugs were predicted, with zoledronic acid showing potential for targeting dual hub genes, offering a promising therapeutic approach for the comorbidity of lung cancer and myocardial infarction.

Keywords: acute myocardial infarction (AMI); bioinformatics analysis; differentially expressed genes (DEGs); hub genes; non-small cell lung cancer (NSCLC).

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Flowchart of the study.
FIGURE 2
FIGURE 2
(A, B) Visualization of DEGs of GSE166780 and GSE8569 using volcano plots, blue represents downregulation, red represents upregulation (|log2(FC)|>1, p < 0.05) (C, D) Visualization of GSE166780 and GSE8569 using box plots (E) Co-expressed upregulated differentially expressed genes (DEGs) of GSE166780 and GSE8569 (|log2(FC)|>1, p < 0.05) (F) Co-expressed downregulated DEGs of GSE166780 and GSE8569 (|log2(FC)|>1, p < 0.05).
FIGURE 3
FIGURE 3
Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of DEGs (A) Biological Processes (B) Cellular Component (C) Molecular Function (D) KEGG.
FIGURE 4
FIGURE 4
Protein-protein interaction (PPI) network of common DEGs.
FIGURE 5
FIGURE 5
(A) PPI network of common DEGs visualized using Cytoscape (B, C) MCODE plugin shows that cluster 1 contains 6 nodes and 14 edges with a score of 5.6. Cluster 2 contains 3 nodes and 3 edges with a score of 3.
FIGURE 6
FIGURE 6
Identification of hub genes (A–D) The top 10 genes in the PPI network were sorted by Degree, MCC, EPC, and MNC respectively. The 8 hub genes identified are CEBPA, TGFBR2, EZH2, JUNB, JUN, FOS, PLAU, COL1A1.
FIGURE 7
FIGURE 7
GO and KEGG analysis of Hub genes (A) Biological Processes (B) Cellular Component (C) Molecular Function (D) KEGG.
FIGURE 8
FIGURE 8
PPI analysis of hub genes using GeneMANIA.
FIGURE 9
FIGURE 9
Diagnostic Receiver operating characteristic (ROC) curves of 8 co-expressed hub genes (A) ROC curve of the hub gene in the GSE8569 dataset. (B) ROC curve of the hub gene in the GSE166780 dataset. (C) ROC curve of the hub gene in the GSE75037 dataset. (D) ROC curve of the hub gene in the GSE34198 dataset.
FIGURE 10
FIGURE 10
(A) TF-Hub genes network, circles are hub genes, and squares are TFs. (B) miRNA-Hub genes network, circles are hub genes, and squares are miRNAs.
FIGURE 11
FIGURE 11
Analysis of hub genes on DGibd, a sum of 145 drugs were discovered. Red indicates hub genes, yellow indicates the top ten drugs, green indicates drugs connected with two genes, and blue indicates other potential drugs.
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