Development of cancer-associated fibroblasts subtype and prognostic model in gastric cancer and the landscape of tumor microenvironment

As the components of the tumor microenvironment (TME), cancer-associated fibroblasts (CAFs) are inextricably linked to cancer development. However, the potential impact of CAFs on gastric cancer (GC) remains unclear, as does the relationship between clinical prognosis and immunotherapy. We identified gene alterations associated with CAFs in 1050 gastric cancer samples from three independent datasets and assessed the correlation between CAFs and clinical characteristics, prognosis, and TME. The CRG-Score was developed and validated for predicting overall survival (OS) in gastric cancer patients and its applicability in immunotherapy. We explored the changes of CAFs-related genes (CRGs) in gastric cancer tissues and evaluated their expression patterns. Two molecular subtypes were identified, and the expression of CRGs was assessed among different subtypes in correlation with prognosis and TME characteristics. The CRG-Score was constructed using differentially expressed genes between the subtypes, and its predictive power was evaluated in gastric cancer patients. Additionally, we developed an accurate nomogram to increase the clinical practicality of CRG-Score. Furthermore, CRG-Score was significantly correlated with tumor mutation burden, microsatellite instability, cancer stem cells, and chemotherapeutic drug sensitivity. CRGs have the potential to influence prognosis, TME, and the clinical features of gastric cancer. This provided new possibilities for improving our understanding of gastric cancer, assessing prognosis, and more effective immunotherapeutic strategies.

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