GBP5 as a prognostic biomarker associated with immune cell infiltration, migration and invasion in clear cell renal cell carcinoma

Treatment of advanced clear cell renal cell carcinoma (ccRCC) primarily involves targeted therapy and immunotherapy, however a number of patients develop treatment resistance. Identifying preferred biomarkers and immune-related therapeutic targets is clinically important for the effective treatment of metastatic ccRCC. Due to the unmet clinical need for novel therapeutic approaches, it is important to explore potential biomarkers and their roles in tumor progression. Although guanylate-binding protein 5 (GBP5) expression is notably upregulated in several cancers and promotes tumor progression, its role in ccRCC remains largely unknown. In the present study, GBP5 expression levels were compared between tumors and adjacent normal tissue using data from the Gene Expression Omnibus, Gene Expression Profiling Interactive Analysis 2 and Tumor Immune Estimation Resource (TIMER) databases. The relationship between GBP5 expression and clinicopathological features, along with its diagnostic and prognostic values, was evaluated using R software and the Kaplan-Meier plotter. Gene Ontology term analysis and gene set enrichment analysis were performed to explore the biological functions of GBP5. The GeneMANIA database was used to investigate the protein-protein interaction networks involving GBP5. The Tumor Immune Single-Cell Hub and TIMER databases were used to evaluate the immune infiltration landscape of ccRCC and the association between GBP5 and immune cell markers. <i>In vitro</i>, GBP5 levels were manipulated in renal cancer cells through silencing or overexpressing GBP5 using lentivirus transfection experiments. The migratory and invasive capabilities of the cells were evaluated using wound-healing and Transwell assays. The GBP5 levels in ccRCC tissues were found to be higher compared with those in adjacent tissues. GBP5 expression was associated with the tumor-lymph node-metastasis classification and pathological stage. Furthermore, elevated GBP5 level was associated with a poor prognosis and demonstrated promising diagnostic value. Bioinformatics analysis of GBP5 suggested its involvement in multiple biological processes and its notable association with tumor-infiltrating immune cells. Cellular experiments demonstrated that GBP5 regulates the migration and invasion of renal cancer cells. Overall, GBP5 shows potential as a prognostic indicator and a candidate target for immunotherapy in patients with ccRCC.