Exploring the Role of GGA2 in Cancer Progression: Pan-Cancer Bioinformatics and Experimental Validation in Prostate Cancer

Cancer remains a significant challenge to global public health. Preliminary studies indicate that the protein Golgi-associated, Gamma-adaptin Ear Containing, ARF Binding Protein 2 (GGA2) may influence various cancers. However, the potential role of GGA2 in oncogenesis remains unknown. We utilized data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) projects to analyze GGA2 expression levels. Genetic variations and protein expression of GGA2 in human tissues were assessed using the cBioPortal. Gene Set Enrichment Analysis (GSEA) provided deeper insights into GGA2's oncogenic functions. Comprehensive analysis of TCGA datasets combined with ESTIMATE and TIMER tools demonstrated significant correlations between GGA2 expression levels and clinical outcomes, survival metrics, genomic instability markers (microsatellite instability (MSI)/tumor mutational burden (TMB)), and immune microenvironment composition. Functional validation in prostate cancer models employed qRT-PCR quantification, immunoblotting verification, and cellular behavior assessments through colony formation, Transwell migration, and wound closure assays. Our findings suggest GGA2 could serve as a prognostic biomarker in various cancers. Abnormal levels of GGA2 promoter methylation and genetic alterations may contribute to its dysregulated expression in some cancers. Distinctly, GGA2 expression correlates with MSI and TMB across different cancers and is linked to the expression of immune checkpoint genes. Functionally, GGA2 is instrumental in inhibiting oncogenic mechanisms by diminishing the proliferation, colony formation, invasion, and migratory capabilities of prostate cancer cells. Our study shows that the oncogenic role of GGA2 in various cancers and GGA2 could be served as a biomarker of PARD.