2203P Uncovering prognostic transcriptomic differences in epithelioid malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is a rare and aggressive disease with poor prognosis. MPM is classified into three histological subtypes: epithelioid, biphasic, and sarcomatoid. This classification does not account for survival differences and intratumor heterogenity, especially for epithelioid MPM (eMPM) that is the most common subtype. The aim of this study is to evaluate transcriptomic differences of eMPM based on prognostic classes. MPM patients with available FFPE tissue were retrospectively and prospectively enrolled at Fondazione IRCCS Istituto Nazionale dei Tumori of Milan and Azianda Sanitaria Universitaria Giuliano Isontina of Trieste between 2006 and 2021 within the granted Italian MOH project, GR-2016-02361229. RNA was automatically extracted and quantified using a fluorometer. Transcriptome was assessed through the 3’DGE method. Patients were divided into three groups based on months (mo) of survival: long survivors (LS) > 36 mo, normal survivors (NS) > 12 and ≤ 36 m, and short survivors (SS) ≤ 12 mo. Evaluation of differential gene expression (GED) between SS and LS was performed for single genes. Moreover, in the same setting, a gene set enrichment analysis (GSEA) was also performed. 125 eMPM cases were enrolled, 90 (72%) males and 35 (28%) females, with a median age at diagnosis of 72 years. At a median follow-up of 88 mo, the median overall survival (OS) was 21 mo. Among patients, 33 were LS, 54 were NS, and 38 were SS. GED showed higher levels of NUF2 and TUBB3, genes involved in the epithelial-mesenchimal-transition (EMT), and a lower expression of ADH1B, PLA2G2A, genes related to metabolism, in SS. EMT, metabolism signature and cell proliferation were confirmed by GSEA analysis as more positively correlated pathways while inflammation and immune response related pathways were negatively correlated in SS. Transcriptomic characterization of eMPM reinforces the hypothesis that cell cycle, EMT and immune components could have an impact on eMPM outcome and could be exploited as therapeutic strategies.