A Novel Discovery of CXCL5 in Prognosis Prediction and Targeted Therapy of Glioblastomas

Abstract

Glioblastoma (GBM) patients face a grim prognosis, with many treatments failing to achieve significant improvements. Recent research has focused on the immunosuppressive environment within GBM tumors. One particular protein, C-X-C chemokine ligand 5 (CXCL5), is highly expressed in various cancers and is known to affect the immune environment, tumor invasion, metastasis, and overall prognosis. In our study, we investigated the role of CXCL5 in the immunosuppressive environment of GBM. We aimed to develop a CXCL5-associated immune prognostic signature (IPS) to predict patient outcomes and identify potential treatments targeting the CXCL5/CXCR2 axis. Initially, we performed enzyme-linked immunosorbent assays (ELISA) on 80 high-grade glioma samples to measure CXCL5 levels. We also analyzed RNA-seq data from 169 GBM samples obtained from the TCGA dataset, dividing them into high (CXCL5_H) and low (CXCL5_L) CXCL5 expression groups. Our analysis revealed that the CXCL5_H group had higher expression of immune-related genes but a poorer prognosis compared to the CXCL5_L group. Using the least absolute shrinkage and selection operator (LASSO) Cox analysis, we constructed a CXCL5-associated IPS, which we confirmed as an independent prognostic factor for GBM through univariate and multivariate Cox analyses. We developed a nomogram based on the three-gene IPS to predict overall survival in GBM patients. Moreover, our study identified the CXCL5/CXCR2 axis as a promising target for GBM treatment. We employed computational techniques to screen for potential inhibitors of this axis and validated their effectiveness in vitro. In conclusion, our study provides a new prognostic model and suggests targeted therapeutic options for GBM by elucidating the role of CXCL5 in the tumor's immunosuppressive environment. This work may pave the way for improved patient outcomes and more effective treatments for this challenging cancer.