Abstract
We designed our study with the aim of conducting a comprehensive analysis of the role that GDF-15 plays in pan-cancer. Multiple databases were used to obtain GDF-15 expression. XIANTAO Academic and Sangerbox were utilized to conduct the diagnostic significance of GDF-15 expression across pan-cancer. The relationships between GDF-15 expression and clinical data, tumor stemness, genomic instability, and tumor prognosis in pan-cancer were evaluated. The interaction between molecules and RNA methylation phenotypes related to GDF-15 were explored. The correlations between GDF-15 expression and immune cell infiltration, immune-related genes, as well as immune checkpoints were also under investigation. Besides, immunohistochemistry (IHC)-based tissue microarray analysis of LUAD validated GDF-15 protein expression and its correlation with survival prognosis. GDF-15 exhibited differential expression across various cancers, being upregulated in BRCA, CHOL, COAD, HNSC, LIHC, LUAD, READ, STAD, THCA, and UCEC, but downregulated in KIRC and LUSC. Its expression correlated with clinical parameters and GDF-15 expression had prognostic value in some cancers. Notably, it had a remarkable diagnostic value in CHOL, COAD, ESCC, GBM, LAML, READ and THCA. GDF-15 was involved in influencing tumor stemness, genomic instability. Besides, GDF-15 interacted with molecules involved in iron ion homeostasis and acute-phase response, receptor activator, ligand activities and cellular senescence. It was intertwined with key tumor processes. Moreover, GDF-15 expression further influenced immune cell infiltration, related immune genes, and immune checkpoints. More importantly, IHC staining results of tissue microarrays confirmed its differential protein expression in LUAD tissues, where elevated levels were significantly associated with poorer overall survival, underscoring its clinical relevance. GDF-15 functioned as a prospective indicator for both the diagnosis and prognosis in various cancers.