GPI: A pan-cancer biomarker integrating genetic alterations, immune infiltration, and therapeutic response prediction.

Glucose-6-phosphate isomerase (GPI) is a key metabolic enzyme implicated in tumorigenesis, yet its pan-cancer role and clinical significance remain incompletely understood. This study aimed to systematically characterize GPI expression, genetic alterations, clinical relevance, and biological functions across cancers, and validate its pro-oncogenic effects.We employed bioinformatics tools (GEPIA2, SangerBox 3.0, cBioPortal, TIMER 2.0, etc.) to analyze GPI expression, genetic alterations, and clinical relevance across multiple cancer types. In vitro experiments were conducted to validate its pro-oncogenic effects in LGG cells.Bioinformatics analyses showed that GPI was upregulated in 29 cancers and downregulated in 3 cancers. High GPI expression was associated with advanced stage, metastasis and poor prognosis. Genetic alterations positively regulated GPI expression, which was linked to cancer stemness, RNA modification, metabolic pathways and tumor immune microenvironment, and could predict chemotherapy response. In vitro experiments confirmed that GPI overexpression promoted LGG cell proliferation, colony formation and invasion, while knockdown inhibited these phenotypes. The correlation between DNA repair and GPI expression is interconnected through metabolic and genetic instability pathways, requiring further investigation.GPI acts as a pan-cancer pro-oncogenic factor and a promising diagnostic, prognostic, and therapeutic biomarker. Further research on its molecular mechanisms, particularly with DNA repair, will inform novel cancer treatment strategies.