AICD-associated MMP1 in ovarian cancer: Prognostic, spatial, and functional evidence

Background Ammonia-induced cell death (AICD) is a recently described form of regulated cell death, but the clinical relevance of AICD-associated genes in ovarian cancer remains unclear. Methods Transcriptomic and clinical data from TCGA-OV and four GEO cohorts were used to evaluate AICD-associated prognostic genes and a fixed 18-gene Ridge model. Public GSE211956 single-cell and Visium data were re-analysed using author-provided cell annotations, preranked gene set enrichment analysis, CellChat, and spatial CD8-neighbourhood permutation testing. Associations between MMP1 expression and CTRP and PRISM dose-response AUC were evaluated. MMP1 knockdown was evaluated in SKOV3 cells. Results The Ridge model showed moderate discrimination in TCGA-OV (1-, 3-, and 5-year AUCs, 0.669, 0.709, and 0.723) and modest external discrimination (C-index range, 0.544-0.583). MMP1 was upregulated in ovarian tumours and associated with poorer survival. In GSE211956, MMP1-detected tumour cells were confined to the Y2 specimen. No immune-related pathway remained significant after false-discovery-rate correction. CellChat predicted stronger fibroblast-to-tumour communication for the MMP1-detected state, but no direct MMP1 ligand-receptor interaction was present in the database. Spatial CD8-related effects were heterogeneous across sections and did not support a consistent immune-exclusion pattern. Higher MMP1 correlated with higher RITA or PX-12 AUC, indicating lower predicted in-vitro sensitivity. MMP1 silencing reduced epithelial-mesenchymal transition, migration, invasion, and proliferation in SKOV3 cells. Conclusion MMP1 is an AICD-associated prognostic marker with experimentally supported oncogenic functions in SKOV3 cells. The immune and pharmacogenomic findings are exploratory and do not establish direct AICD regulation, immune exclusion, or clinical drug-response prediction.