DEPP1: A prognostic biomarker linked to stroma‑rich and immunosuppressive microenvironment, promoting oxaliplatin resistance in gastric cancer

Decidual protein induced by progesterone (DEPP1) was identified to exert heterogeneous functions in several cancers, whereas its role in gastric cancer (GC) remains elusive. In the present study, differential expression analysis was conducted using three Gene Expression Omnibus datasets (GSE54129, GSE26942 and GSE3438). Validation of DEPP1 expression was performed using reverse transcription‑quantitative PCR, western blotting and immunofluorescence. Kaplan‑Meier survival and Cox regression analyses were employed to assess the association between DEPP1 expression and the prognosis of patients with GC. Immune infiltration analysis was conducted to explore the correlation between DEPP1 and the tumor microenvironment. The potential of DEPP1 to promote oxaliplatin resistance was assessed using flow cytometry, western blotting, and subcutaneous mouse models. DEPP1 was found to be significantly upregulated in the aforementioned cohorts, which was consistent with the clinical specimens of the present study, and it emerged as an independent risk factor for poor overall survival in patients with GC. A prognostic nomogram was developed to improve prognosis prediction. High DEPP1 expression correlated with increased infiltration of cancer‑associated fibroblasts, endothelial cells, and M2 macrophages, contributing to the development of a stroma‑rich and immunosuppressive microenvironment in GC. Furthermore, high DEPP1 expression was associated with reduced sensitivity to chemotherapy drugs in patients with GC. <i>In vitro</i> and <i>in vivo</i> experiments highlighted DEPP1's crucial role in promoting oxaliplatin resistance in GC. In conclusion, DEPP1 is identified as a promising prognostic biomarker linked to a stroma‑rich and immunosuppressive microenvironment, and it is critical in driving oxaliplatin resistance in GC. These findings may inform personalized therapeutic strategies for patients with GC.