Abstract
Malignant pleural mesothelioma (MPM) is a rare and aggressive neoplasm of the pleural tissue that lines the lungs and is mainly associated with long latency from asbestos exposure. This tumor has no effective therapeutic opportunities nowadays and has a very low five-year survival rate. In this sense, identifying molecular events that trigger the development and progression of this tumor is highly important to establish new and potentially effective treatments. We conducted a meta-analysis of genome-wide expression studies publicly available at the Gene Expression Omnibus (GEO) and ArrayExpress databases. The differentially expressed genes (DEGs) were identified, and we performed functional enrichment analysis and protein–protein interaction networks (PPINs) to gain insight into the biological mechanisms underlying these genes. Additionally, we constructed survival prediction models for selected DEGs and predicted the minimum drug inhibition concentration of anticancer drugs for MPM. In total, 115 MPM tumor transcriptomes and 26 pleural tissue controls were analyzed. We identified 1046 upregulated DEGs in the MPM samples. Cellular signaling categories in tumor samples were associated with the TNF, PI3K-Akt, and AMPK pathways. The inflammatory response, regulation of cell migration, and regulation of angiogenesis were overrepresented biological processes. Expression of SOX17 and TACC1 were associated with reduced survival rates. This meta-analysis identified a list of DEGs in MPM tumors, cancer-related signaling pathways, and biological processes that were overrepresented in MPM samples. Some therapeutic targets to treat MPM are suggested, and the prognostic potential of key genes is shown.
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All data used in this study are publicly available at the GEO (GSE42977 and GSE12345) and ArrayExpress (E-MTAB-47 and E-MTAB-6877) repositories.
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Acknowledgements
This study received funds from the Dirección Nacional de Investigaciones, Fundación Universitaria del Área Andina, Bogotá, Colombia.
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This work was supported by the Dirección Nacional de Investigaciones, Fundación Universitaria del Área Andina, Bogotá, Colombia (Grant No. CV2022-CSD-B-12516).
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Conceptualization: CO, DAF, AM-G, DAB, CMR, FE-D, and ALC. Data collection and computational analysis: CO, AM-G, DAB, and DAF. Data curation: CO; AM-G. Original draft preparation: AM-G, DAB, CMR, FE-D, ALC, DAF, CO. Writing final manuscript: CO; AM-G; DAB; DAF; ALC. All authors read and approved the final manuscript.
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Supplementary file2 (DOCX 142 KB) Supplementary Fig. 2. Volcano plot representing all upregulated (red dots) and downregulated (blue dots) DEGs identified in the meta-analysis.
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Supplementary file3 (DOCX 1872 KB) Supplementary Fig. 3. Graph-based clustering of the protein–protein interaction networks of upregulated DEGs.
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Supplementary file4 (XLSX 51 KB) Supplementary Table S1. Upregulated DEGs in human MPM tumors compared to pleural tissues.
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Supplementary file5 (XLSX 109 KB) Supplementary Table S2. Top downregulated DEGs in human MPM tumors compared to pleural tissues.
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Supplementary file6 (XLSX 25 KB) Supplementary Table S3. Top-ranked terms after functional enrichment analysis of upregulated DEGs.
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Supplementary file7 (XLSX 13 KB) Supplementary Table S4. Interaction of upregulated DEGs in human MPM tumors with known drugs.
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Mejia-Garcia, A., Bonilla, D.A., Ramirez, C.M. et al. Genes and Pathways Involved in the Progression of Malignant Pleural Mesothelioma: A Meta-analysis of Genome-Wide Expression Studies. Biochem Genet 62, 352–370 (2024). https://doi.org/10.1007/s10528-023-10426-5
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DOI: https://doi.org/10.1007/s10528-023-10426-5