Characterizing the Tumor Microenvironment and Its Correlation with cDC1-Related Gene Expression in Gastric Cancer

Abstract

Background and Aim. Gastric cancer (GC) remains a significant global health challenge. The role of conventional type 1 dendritic cells (cDC1s) in the tumor microenvironment and their association with cancer prognosis is gaining attention. This study aims to evaluate the prognostic value of cDC1-related genes (CD141, XCR1, CLEC9A, CADM1, and BTLA) in GC and explore their underlying biological mechanisms. Materials and Methods. We analyzed RNA-seq data from the Cancer Genome Atlas (TCGA-STAD) and Gene Expression Omnibus (GEO) datasets, focusing on five cDC1-related genes. The cDC1-related signature was defined and divided into high and low expression groups. We employed gene set variation analysis (GSVA) for oncogenic signaling pathways and conducted comprehensive statistical analyses, including Kaplan–Meier and Cox proportional hazards models. Results. The high cDC1-related gene signature group was associated with poorer overall and disease-free survival in the TCGA-STAD cohort. Significant differences in CD8+ T cell infiltration and cytotoxic capabilities were observed between high and low CDC1-related signature groups. The study also revealed a strong correlation between CDC1-related signature and increased expression of immune checkpoint proteins and oncogenic pathways, suggesting a complex immunosuppressive tumor microenvironment. Conclusions. Our findings indicate the potential of the cDC1-related signature as a prognostic marker in GC, offering insights into the tumor–immune interplay. The study underscores the importance of cDC1s in shaping the tumor microenvironment and their influence on patient prognosis in GC. These results may contribute to the development of novel therapeutic strategies targeting the immune microenvironment in GC.