DZIP1 expressed in fibroblasts and tumor cells may affect immunosuppression and metastatic potential in gastric cancer.

Abstract

The tumor microenvironment (TME) contains complex components, of which the most well-known one is the tumor-associated fibroblast (CAF) that participates in the development and progression of tumors. A high abundance of CAFs implies that tumor stroma is also abundant and often predicts a poor prognosis, especially in terms of immunotherapeutic resistance. In this study, DAZ interacting zinc finger protein 1 (DZIP1) was identified to be upregulated in CAFs and malignant epithelial cells based on single-cell sequencing. Furthermore, results from The Cancer Genome Atlas database showed that this gene was highly positively associated with the mesenchymal phenotype in gastric cancer (GC). In addition, molecular experiments verified that DZIP1 directly promoted the proliferation of CAFs and enhanced the epithelial-mesenchymal transition (EMT) of GC cells to drive angiogenesis. Also, the upregulated DZIP1 in GC cells was found to directly promote invasion and metastasis. Finally, multiplex immunofluorescence and immunohistochemistry showed that DZIP1 was correlated with the immunosuppressive microenvironment of GC and resulted in a poor response to immunotherapy. Overall, our findings suggest that DZIP1 is expressed in both tumor parenchyma and mesenchyme and that it is involved in shaping the immunosuppressive microenvironment and inducing EMT by participating in tumor-stromal signaling crosstalk.