Identification of Overexpressed Genes in Malignant Pleural Mesothelioma
Malignant pleural mesothelioma (MPM) is a fatal tumor lacking effective therapies. The characterization of overexpressed genes could constitute a strategy for identifying drivers of tumor progression as targets for novel therapies. Thus, we performed an integrated gene-expression analysis on RNAseq...
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| Format: | Article |
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MDPI AG
2021-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/5/2738 |
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| author | Federica Morani Luisa Bisceglia Giulia Rosini Luciano Mutti Ombretta Melaiu Stefano Landi Federica Gemignani |
| author_facet | Federica Morani Luisa Bisceglia Giulia Rosini Luciano Mutti Ombretta Melaiu Stefano Landi Federica Gemignani |
| author_sort | Federica Morani |
| collection | DOAJ |
| description | Malignant pleural mesothelioma (MPM) is a fatal tumor lacking effective therapies. The characterization of overexpressed genes could constitute a strategy for identifying drivers of tumor progression as targets for novel therapies. Thus, we performed an integrated gene-expression analysis on RNAseq data of 85 MPM patients from TCGA dataset and reference samples from the GEO. The gene list was further refined by using published studies, a functional enrichment analysis, and the correlation between expression and patients’ overall survival. Three molecular signatures defined by 15 genes were detected. Seven genes were involved in cell adhesion and extracellular matrix organization, with the others in control of the mitotic cell division or apoptosis inhibition. Using Western blot analyses, we found that ADAMTS1, PODXL, CIT, KIF23, MAD2L1, TNNT1, and TRAF2 were overexpressed in a limited number of cell lines. On the other hand, interestingly, CTHRC1, E-selectin, SPARC, UHRF1, PRSS23, BAG2, and MDK were abundantly expressed in over 50% of the six MPM cell lines analyzed. Thus, these proteins are candidates as drivers for sustaining the tumorigenic process. More studies with small-molecule inhibitors or silencing RNAs are fully justified and need to be undertaken to better evaluate the cancer-driving role of the targets herewith identified. |
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| format | Article |
| id | doaj.art-c7a9346552b14159aa0b065b5ed3d0e5 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T13:26:27Z |
| publishDate | 2021-03-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c7a9346552b14159aa0b065b5ed3d0e52023-11-21T09:38:45ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-03-01225273810.3390/ijms22052738Identification of Overexpressed Genes in Malignant Pleural MesotheliomaFederica Morani0Luisa Bisceglia1Giulia Rosini2Luciano Mutti3Ombretta Melaiu4Stefano Landi5Federica Gemignani6Department of Biology, University of Pisa, 56126 Pisa, ItalyDepartment of Biology, University of Pisa, 56126 Pisa, ItalyDepartment of Biology, University of Pisa, 56126 Pisa, ItalyCenter for Biotechnology, Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University, Philadelphia, PA 19122, USADepartment of Biology, University of Pisa, 56126 Pisa, ItalyDepartment of Biology, University of Pisa, 56126 Pisa, ItalyDepartment of Biology, University of Pisa, 56126 Pisa, ItalyMalignant pleural mesothelioma (MPM) is a fatal tumor lacking effective therapies. The characterization of overexpressed genes could constitute a strategy for identifying drivers of tumor progression as targets for novel therapies. Thus, we performed an integrated gene-expression analysis on RNAseq data of 85 MPM patients from TCGA dataset and reference samples from the GEO. The gene list was further refined by using published studies, a functional enrichment analysis, and the correlation between expression and patients’ overall survival. Three molecular signatures defined by 15 genes were detected. Seven genes were involved in cell adhesion and extracellular matrix organization, with the others in control of the mitotic cell division or apoptosis inhibition. Using Western blot analyses, we found that ADAMTS1, PODXL, CIT, KIF23, MAD2L1, TNNT1, and TRAF2 were overexpressed in a limited number of cell lines. On the other hand, interestingly, CTHRC1, E-selectin, SPARC, UHRF1, PRSS23, BAG2, and MDK were abundantly expressed in over 50% of the six MPM cell lines analyzed. Thus, these proteins are candidates as drivers for sustaining the tumorigenic process. More studies with small-molecule inhibitors or silencing RNAs are fully justified and need to be undertaken to better evaluate the cancer-driving role of the targets herewith identified.https://www.mdpi.com/1422-0067/22/5/2738malignant pleural mesotheliomaMPMRNAseqgene signatureoverexpressed genestherapeutic targets |
| spellingShingle | Federica Morani Luisa Bisceglia Giulia Rosini Luciano Mutti Ombretta Melaiu Stefano Landi Federica Gemignani Identification of Overexpressed Genes in Malignant Pleural Mesothelioma International Journal of Molecular Sciences malignant pleural mesothelioma MPM RNAseq gene signature overexpressed genes therapeutic targets |
| title | Identification of Overexpressed Genes in Malignant Pleural Mesothelioma |
| title_full | Identification of Overexpressed Genes in Malignant Pleural Mesothelioma |
| title_fullStr | Identification of Overexpressed Genes in Malignant Pleural Mesothelioma |
| title_full_unstemmed | Identification of Overexpressed Genes in Malignant Pleural Mesothelioma |
| title_short | Identification of Overexpressed Genes in Malignant Pleural Mesothelioma |
| title_sort | identification of overexpressed genes in malignant pleural mesothelioma |
| topic | malignant pleural mesothelioma MPM RNAseq gene signature overexpressed genes therapeutic targets |
| url | https://www.mdpi.com/1422-0067/22/5/2738 |
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