[Prognostic significance and immune cell infiltration analysis of differentially expressed genes in malignant pleural mesothelioma].

ABSTRACT

Objective: To explore and analyze differential expressed genes in malignant pleural mesothelioma (MPM) by bioinformatics method, and to study their prognostic value in MPM and their potential role in immunotherapy. Methods: In January 2022, the dataset GSE51024 was downloaded from the GEO database, and MPM (55 cases) and normal tissue (41 cases) samples were obtained. Using R software and HMDD and miRNet database, MPM-related differential genes were screened and co-expressed genes were identified. Co-expressed genes were enriched and functionally annotated, and protein-protein interaction (PPI) networks were constructed and key genes were identified using the STRING database and Cytoscape software. TRRUST and GEPIA databases were used to predict transcription factors of key genes and to analyze prognosis and survival. The correlation between key genes and the degree of infiltration of immune cells was analyzed using TIMER. Results: A total of 435 co-expressed genes were obtained, which were mainly concentrated in the extracellular matrix tissue and the signaling pathways of cell adhesion molecules. Combined with PPI and TRRUST database, seven key MPM prognostic genes were identified. Among them, cyclin 20 (CDC20) , cell cycle checkpoint kinase 1 (CHEK1) , enhancer of Zeste homolog 2 (EZH2) , ribonucleotide reductase subunit M2 (RRM2) , topoisomerase 2A (TOP2A) , ubiquitin like plant homeodomain and ring finger domain 1 (UHRF1) were significantly up-regulated in MPM, while cyclin A1 (CCNA1) was significantly down-regulated. The expressions of CCNA1, CDC20, CHEK1, EZH2, RRM2, TOP2A and UHRF1 genes were significantly associated with MPM overall survival (P<0.05) . The expressions of CDC20, CHEK1, EZH2, RRM2 and TOP2A genes were positively correlated with B cells and dendritic cells (P<0.05) , and negatively correlated with neutrophils (P<0.05) . Conclusion: CCNA1, CDC20, CHEK1, EZH2, RRM2, TOP2A and UHRF1 may be potential prognostic markers in MPM patients, and their expressions may be related to MPM tumor immunity.