TIMP1: A novel immune-related signature associated with invasiveness and inhibition of pituitary adenoma

The invasiveness of pituitary adenomas is closely related to the tumour immune microenvironment. This study aimed to identify immune-related genes associated with IPAs. Transcriptomic data from 32 patient-derived samples were analysed to screen immune-related differentially expressed genes between IPAs and non-invasive pituitary adenomas. Weighted gene co-expression network analysis of merged datasets (GSE26966 and GSE51618) was performed to identify hub genes, which were then intersected with immune-related DEGs. Least absolute shrinkage and selection operator regression and support vector machine algorithms consistently identified tissue inhibitor of metalloproteinases 1 (TIMP1) as a key immune-associated invasive gene. Multi-omics validation confirmed significant downregulation of TIMP1 in IPAs. Functional enrichment, single-sample gene set enrichment analysis, CIBERSORT, and immune checkpoint profiling linked TIMP1 to macrophage infiltration and immune regulation. Immunohistochemistry and in vitro experiments further demonstrated that TIMP1 overexpression inhibited tumour-cell proliferation, invasion, and migration. Collectively, these findings suggest that TIMP1 downregulation may promote IPA progression through immune dysregulation.