Identification of Overexpressed Genes in Malignant Pleural Mesothelioma

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.

A panel of emerging EMT genes identified in malignant mesothelioma

“…Therefore, regulation of each individual gene expression and its signalling pathways might potentially control EMT process thus leading to development of novel strategies for MESO therapeutics. SPARC protein has been observed upregulated in MESO cell lines 46 . Transcriptomic studies have identified that EMT-linked genes may contribute towards the resistance of chemotherapy and immunotherapy, suggesting that targeting EMT genes may be potentially applied to treat MESO patients 47 .…”

Case report: Mesothelioma and BAP1 tumor predisposition syndrome: Implications for public health

“…BAP1 may also be a possible therapeutic target for precision medicine and prognostic biomarkers, being frequently altered in MM ( 29 ) together with other targets reported thus far ( 30 , 31 ). The 15th conference of the International Mesothelioma Interest Group (iMig), held in May 2021, demonstrated the usefulness of pleural effusions for the early diagnosis of MM.…”

Identification of Novel Diagnostic Markers for Malignant Pleural Mesothelioma Using a Reverse Translational Approach Based on a Rare Synchronous Tumor

“…No previous report has indicated that MPM expresses PHGDH or TRIM29 [ 12 , 13 , 18 ]. Nevertheless, both PHGDH and TRIM29 showed better immunohistochemical specificity and sensitivity than expected, despite the use of antibodies that are not really suited for routine FFPE immunohistochemistry.…”

“…In recent years, gene expression profiling (GEP) technology has become a key tool for the discovery of novel biomarkers [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ], and it is readily applicable for analysis based on formalin-fixed paraffin-embedded (FFPE) tissues [ 14 , 15 ]. We have encountered a very rare example of a synchronous collision tumor consisting of both malignant pleural mesothelioma (MPM) and pulmonary adenocarcinoma (PAC) lesions, each of which showed the typical morphology and immunophenotype.…”