Depp1 Emerges as a Prognostic Biomarker Associated with Stroma-Rich and Immunosuppressive Microenvironment and Predicts Poor Chemotherapy Response in Gastric Cancer

Abstract

BackgroundDecidual protein induced by progesterone (DEPP1) was identified to exert heterogeneous functions in various cancers, whereas its role in GC remains elusive.MethodsDifferential expression analysis was applied based on three Gene Expression Omnibus datasets. Quantitative real-time PCR, western blotting, and immunofluorescence were employed to verify the expression pattern of the selected gene. The Kaplan-Meier survival and Cox regression analyses were conducted to explore its association with GC patients’ prognosis. The correlation between DEPP1 and tumor microenvironment was analyzed via immune infiltration analysis. The ability of this gene to predict the sensitivity of GC patients to chemotherapy agents was predicted via the “oncoPredict” R package.ResultsDEPP1 was uncovered as a significantly upregulated gene in the GSE54129, GSE26942, and GSE3438 cohorts, which was corroborated in our clinical specimens. It was demonstrated to be an independent risk factor and predicted poor overall survival of GC patients. Then, we established a prognostic nomogram to better predict the prognosis of GC patients. High expression of DEPP1 was significantly associated with increased infiltration levels of cancer-associated fibroblasts, endothelial cells, and M2 macrophages, suggesting DEPP1 as an essential regulator contributing to the development of stroma-rich and immunosuppressive microenvironment of GC. Finally, we determined that high expression of DEPP1 correlated with reduced sensitivity of GC patients to chemotherapy drugs.ConclusionsThis study highlights DEPP1 as a promising prognostic biomarker associated with stroma-rich and immunosuppressive microenvironment and predicts poor chemotherapy response, which might provide novel insights into the individual therapeutic approaches for GC.

Note:
Funding Information: This work was supported by the National Natural Science Foundation of China (Grant No. 82072669 and 81702303) and CSCO-Zaiding Cancer Research Fund (Grant No. Y-zai2021/ms-0228).

Declaration of Interests: The authors declare that they have no competing interests.

Ethics Approval Statement: This study was carried out in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine (No. KY2021-252-B). All the patients enrolled in this study provided written informed consent.

Keywords: Gastric Cancer, DEPP1, Prognostic biomarker, tumor microenvironment, chemotherapy