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

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Cancer poses a significant global health challenge.
• The protein Golgi-associated, Gamma-adaptin Ear Containing, ARF Binding Protein 2 (GGA2) is implicated in various cancers, but its role in oncogenesis is unclear.

Purpose of the Study:

• To investigate the role of GGA2 in oncogenesis and its potential as a prognostic biomarker across diverse cancers.
• To analyze GGA2 expression, its correlation with clinical outcomes, genomic instability, and the tumor immune microenvironment.

Main Methods:

• Utilized The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases for expression analysis.
• Assessed genetic variations and protein expression via cBioPortal; employed Gene Set Enrichment Analysis (GSEA).
• Correlated GGA2 levels with clinical data, microsatellite instability (MSI), tumor mutational burden (TMB), and immune markers using ESTIMATE and TIMER tools. Validated findings in prostate cancer models.

Main Results:

• GGA2 expression significantly correlates with clinical outcomes, survival rates, MSI/TMB, and immune microenvironment composition in various cancers.
• Aberrant GGA2 promoter methylation and genetic alterations contribute to its dysregulation.
• GGA2 expression is linked to immune checkpoint genes and functionally inhibits prostate cancer cell proliferation, migration, and invasion.

Conclusions:

• GGA2 serves as a potential prognostic biomarker for multiple cancer types.
• GGA2's oncogenic role is confirmed, with its expression linked to genomic instability and immune responses.
• GGA2 functions to suppress tumorigenesis by reducing cancer cell proliferation and invasiveness.