Immune landscape and prognostic gene signatures in gastric cancer: implications for cachexia and clinical outcomes

Abstract

Cachexia, a debilitating condition that worsens patient outcomes, often accompanies gastric cancer, a malignancy that is prevalent worldwide. The extensive research explored the interconnected molecular and immune aspects of stomach cancer, with a particular emphasis on cachexia. By employing the GEO database, we identified genes that were expressed differently in gastric cancer patients suffering from cachexia. Following the analysis of Weighted Gene Co-expression Network (WGCNA), gene modules intricately linked to particular immune cells were revealed, indicating a significantly disrupted tumor microenvironment. A strong predictive model was developed, centered around key genes such as CAMK4, SLC37A2, and BCL11B. Surprisingly, this particular model not only showed better predictive abilities in comparison to conventional clinical factors but also exhibited a strong connection with increased infiltration of macrophages and T cells. These discoveries suggest the presence of an immune-suppressing and tumor-promoting atmosphere among individuals at a greater risk. Moreover, the utilization of Gene Set Enrichment Analysis (GSEA) established a connection between the genes linked to our risk score and vital immune-related pathways, thereby strengthening the pivotal involvement of immunity in the development of gastric cancer. To summarize, our discoveries provide a more profound comprehension of the molecular and immune mechanisms that support cachexia in gastric cancer, presenting a hopeful basis for upcoming advancements in treatment.