The role of CD101 and Tim3 in the immune microenvironment of gastric cancer and their potential as prognostic biomarkers

Background: Gastric cancer (GC) is a prevalent malignancy. Current treatment modalities, including surgery, chemotherapy, radiotherapy, and targeted therapy, have limitations in early detection and personalized treatment, necessitating the discovery of novel biomarkers and therapeutic strategies. This study aims to elucidate the molecular mechanisms underlying GC, focusing on the differentially expressed genes (DEGs) of CD101^- Tim3⁺ CD8⁺ T cells (CCT precursors) and CD101⁺ Tim3⁺ CD8⁺ T cells (CCT).

Methods: Utilizing a multi-omics approach, including transcriptomic sequencing, single-cell RNA sequencing, cell communication analysis, and enrichment analysis.

Results: We identified 140 genes significantly associated with overall survival in GC patients, including LYAR, ASCL2, and EMP2. A risk score model based on 14 prognostic genes was constructed, demonstrating a significant inverse correlation with survival time (p < 0.05). Immune response analysis indicated decreased infiltration of Activated B cells, CD56bright natural killer cells, and Monocytes in the high-risk group, while CD56dim natural killer cells and Gamma delta T cells were significantly increased, suggesting alterations in the immune microenvironment that influence patient prognosis. Furthermore, drug sensitivity analysis revealed potential responsiveness of high-risk patients to BI-2536, supporting personalized treatment approaches. Cell communication analysis indicated reduced intercellular interactions in PD-1 immunotherapy groups, highlighting the impact of immunotherapy on the tumor microenvironment. GSEA (Gene Set Enrichment Analysis) and GSVA (Gene Set Variation Analysis) revealed enrichment in DNA replication and proteasome pathways in high-risk groups, providing insights into the molecular mechanisms of GC.

Conclusions: This study established a foundation for future exploration of targeted therapies and personalized treatment strategies in GC.