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.

Morani, F., Bisceglia, L., Rosini, G., Mutti, L., Melaiu, O., Landi, S., et al. (2021). Identification of overexpressed genes in malignant pleural mesothelioma. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 22(5), 1-17 [10.3390/ijms22052738].

Identification of overexpressed genes in malignant pleural mesothelioma

Melaiu O.;
2021

Abstract

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.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/05
English
MPM
RNAseq
gene signature
malignant pleural mesothelioma
overexpressed genes
therapeutic targets
Female
Humans
Male
Gene Expression Regulation, Neoplastic
Mesothelioma, Malignant
Neoplasm Proteins
Pleural Neoplasms
Morani, F., Bisceglia, L., Rosini, G., Mutti, L., Melaiu, O., Landi, S., et al. (2021). Identification of overexpressed genes in malignant pleural mesothelioma. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 22(5), 1-17 [10.3390/ijms22052738].
Morani, F; Bisceglia, L; Rosini, G; Mutti, L; Melaiu, O; Landi, S; Gemignani, F
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/305964
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