GBP2 promotes clear cell renal cell carcinoma progression through immune infiltration and regulation of PD-L1 expression via STAT1 signaling

Abstract

Guanylate-binding protein 2 (GBP2) has been widely studied in cancer, however, its potential role in clear cell renal cell carcinoma (ccRCC) is not fully elucidated. The present study aimed to explore the effect of GBP2 on tumor progres- sion and its possible underlying molecular mechanisms in ccRCC. The Cancer Genome Atlas, Gene Expression Omnibus, Cancer Cell Line Encyclopedia databases, and several bioin- formatics analysis tools, such as Gene Expression Profiling Interactive Analysis 2, Kaplan-Meier plotter, UALCAN, LinkedOmics, Metascape, GeneMANIA and Tumor Immune Estimation Resource, were used to characterize the functional relationship between GBP2 and ccRCC. Focusing on the association between GBP2 and programmed death ligand 1 (PD-L1) in vitro, the regulatory mechanism was investigated by knockdown and overexpression of GBP2 in Caki-1 and 786-O cells using reverse transcription-quantitative PCR, western blotting and co-immunoprecipitation techniques. The results indicated that GBP2 was commonly upregulated in ccRCC, correlating with worse prognosis. In addition, GBP2 expression levels were positively associated with different patterns of immune cell infiltration, suggesting that the GBP2 gene regulates PD-L1 expression via the signal transducer and activator of transcription 1 (STAT1) pathway. The present study suggested that GBP2 regulates tumor immune infiltration and promotes tumor immune escape through PD-L1 expression, revealing a potential immunotherapeutic target for ccRCC.