Chemokine and Receptor Family Gene-Based Prognostic Signature for Predicting Clinical Outcomes and Treatment Response in Glioblastoma

Abstract

Background: Chemokines and receptor (CCR) genes are closely associated with tumorigenesis and progression. However, their function in the malignant progression of glioblastoma (GBM) is unknown. The present study aims to reveal prognostic factors, molecular subtypes, and prognostic indicators in chemokine genes and receptor genes in GBM. Methods: In this study, expression profiles in The Cancer Genome Atlas (TCGA), The Chinese Glioma Genome Atlas (CGGA), and University of Cingifornia Sisha Cruz (UCSC xnea) were utilized for expression analysis of chemokine/receptor genes in pan-cancer and GBM. Univariate COX models identified chemokine/receptor genes with prognostic value. Chemokine/receptor-related gene types in GBM were determined by consistency clustering analysis. This study constructed a prognostic model (CCR Score) using differentially expressed genes (DEGs) between genotypes. Differences between prognosis, tumor mutation burden (TMB), immune checkpoint genes, tumor microenvironment (TME), and drug sensitivity were explored in CCR Score groups and gene types. Results: Expression models of chemokine/receptor genes were explored, and two differentially characterized genotypes (CCR1 and CCR2) were identified in pan-cancer and GBM. CCR1 and CCR2 exhibited different prognoses, TMB, and TME activity. RTK-RAS (56.2%), PI3K (50.4%), TP53 (30.8%), NOTCH (28.8%), and Hippo (25.2%) pathways had a higher percentage of variants. Next, based on the DEGs in CCR1 and CCR2, we constructed a prognostic model (CCR Score) for predicting the prognosis of GBM patients. The CCR Score showed excellent prognostic and predictive performance, and patients with high CCR Score and CCR1 showed better immune activity and were more sensitive to immunotherapy. In addition, the CCR Score was significantly correlated with cancer chemotherapy sensitivity. Conclusion: Overall, we identified the CCR characteristics of GBM patients prognosis, and the CCR Score helps elucidate the potential link between GBM progression and chemokines/receptors and helps explore the mechanisms of carcinogenesis and therapeutic strategies.