Identification of Overexpressed Genes in Malignant Pleural Mesothelioma.

Federica Morani,Giulia Rosini,Luisa Bisceglia,Stefano Landi,Luciano Mutti,Federica Gemignani,Ombretta Melaiu

doi:10.3390/ijms22052738

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.

Highlights

In the attempt to detect genes that play a role in determining the malignant phenotype and that could be exploited as possible therapeutic targets, many studies were carried out with the use of microarrays
We are aware that this type of reference sample was not optimal; this step was only used for a first analysis for a mild reduction of the number of genes
We went deep into the Supplementary Materials available for this study and selected genes showing any extent of differential expression, provided it was statistically significant, and we considered the genes showing evidence of being differentially expressed in Malignant pleural mesothelioma (MPM) in at least one study

Summary

Introduction

Malignant pleural mesothelioma (MPM) is a rare cancer of the pleura caused by a past exposure to asbestos. The patients’ median overall survival (OS) is

Methods

Results

Discussion

Conclusion