Abstract
Malignant pleural mesothelioma (MPM) is a rare but highly aggressive thoracic malignancy. ESTIMATE algorithm-derived immune scores are commonly used to quantify the immune and stromal components in tumors. Thus, this algorithm may help determine the tumor microenvironment (TME)-related gene expression profile associated with tumor immunity. This study aimed at mining public databases to determine a potential correlation between differentially expressed genes (DEGs) and survival in patients with MPM. We categorized patients from the Gene Expression Omnibus database according to their immune/stromal scores into high- and low-score groups. Functional enrichment analysis and the construction of protein–protein interaction networks showed that the DEGs identified were primarily involved in the TME. Furthermore, we validated these genes in an independent cohort of patients with MPM from The Cancer Genome Atlas database. DEG analysis showed that 29 DEGs were cancer driver genes. Subsequently, 14 TME-related genes, which have been previously neglected, were shown to exhibit significant prognostic potential in MPM. In conclusion, immune/stromal scores are novel predictors of a poor prognosis in patients with MPM. We identified DEGs that are involved in immunity against MPM and may contribute to patient survival. Owing to their potential as prognostic factors for MPM, these 14 TME-related genes need to be studied in detail in the future.
Highlights
Malignant pleural mesothelioma (MPM) is a highly aggressive thoracic malignancy, with three major histological subtypes, namely, epithelioid, sarcomatoid, and biphasic mesotheliomas
Comparison of patients with high and low immune or stromal scores led to the identification of 74 stromal and immune cell-associated differentially expressed genes (DEGs) in the Gene Expression Omnibus (GEO) database
Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that all 74 genes were associated with the tumor microenvironment (TME)
Summary
Malignant pleural mesothelioma (MPM) is a highly aggressive thoracic malignancy, with three major histological subtypes, namely, epithelioid, sarcomatoid, and biphasic mesotheliomas. Several clinical trials have evaluated the efficacy and safety of immunotherapy in patients with MPM [1, 3, 11, 12]. The KEYNOTE-028 trial [1] showed potential clinical benefits of pembrolizumab, an anti-PD-L1 monoclonal antibody, in patients with MPM showing positive PD-L1 expression. The potential therapeutic benefit of combination immunotherapy (CTLA-4 and PD-L1 blockade) against MPM is under investigation, and far, the data from the CheckMate743 (ClinicalTrials.gov Identifier: NCT02899299) and NIBITMESO-1 trials seem promising [3]. There are only a few ongoing trials using a combination of immunotherapy and chemotherapy or surgery, or both, in patients with MPM. The DREAM trial is a multicenter, single-arm, open-label phase II study that aims to determine the effects of durvalumab in combination with chemotherapy for the treatment of MPM. Based on the data presented at the 2018 American Society of Clinical Oncology Conference, the therapeutic efficacy of this regimen seems promising
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