A Novel MALT1-related Immune Prognostic Signature and Targeted Drug Screening for Glioblastoma

Abstract

Abstract As the most common intracranial malignancy in adults, glioblastoma (GBM) has limited improvement in prognosis with traditional treatment methods, such as surgery, chemotherapy, and radiotherapy. Currently, immunotherapy has revolutionized treatment outcomes for many cancers. However, special immunosuppressive microenvironment of GBM results in patients’ resistance to immunotherapy and poor prognosis. The mucosa-associated lymphoid tissue translocation gene 1 (MALT1) was reported to be involved in NF-κB activation and promote cancer cell’s proliferation and migration. And inhibition of MALT1 could attenuate the mesenchymal phenotype of GBM. Therefore, uncovering the role of MALT1 in the immunosuppressive microenvironment of GBM is of great importance. In this study, RNA-seq data of 169 GBM patients were downloaded from TCGA (The Cancer Genome Atlas) database and divided into MALT1_H (MALT1_High) and MALT1_L (MALT1_Low) groups based on MALT1’s expression level. First, the enrichment levels of the 29-immune signature were quantified in every GBM patient of MALT1_H and MALT1_L. Next, DEIGs (differentially expressed immune genes) were identified and used to establish an IPS (immune prognostic signature) by the LASSO (Least Absolute Shrinkage and Selection Operator) Cox regression analysis. PDYN was first found to be associated with GBM prognosis and was identified as a potential target of GBM. Based on three-gene IPS, we developed a predictive nomogram model to assess the prognosis of GBM patients. Additionally, MALT1 were proved to be a potential ideal therapeutic target for GBM. So, series of computer-aided technology were applied to screen favorable inhibitors of MALT1. In summary, we explored role of MALT1 in the suppressive immune microenvironment of GBM, established a novel MALT1-related nomogram model for prognostic prediction, and developed the targeted therapy for GBM in this study.