Expression Patterns of Histone Modification Regulators Predict Prognosis and Microenvironment Characteristics in Gastric Cancer

Multiple studies have demonstrated a significant correlation between histone modifications and tumour initiation and progression. However, it remains unclear whether the histone modification profile contributes to the classification of patients with gastric cancer (GC). After analysing transcriptomic data from 76 histone modification regulators (HMR), we identified four distinct patterns in 838 GC specimens. These patterns demonstrated associations with different prognoses, treatment responses, biological pathways, and tumour microenvironment characteristics. Therefore, we used the Least Absolute Shrinkage and Selection Operator (LASSO) regression and multivariate Cox regression analysis to explore GC's histone modification regulator characteristics and established a 10-gene scoring scheme named "Histone Modification Regulator-based Risk Score (HR_score)" to cluster tumours into high- and low-risk subtypes. Patients with high scores are characterised by increased stromal cell infiltration and exhibit the activation of innate immunity. These observations may be linked to the immune-exclusion phenotype and a poor prognosis. Further analysis revealed a direct correlation between higher HR_score and diminished response to adjuvant chemotherapy and immunotherapy treatments. In summary, this study indicates that HR_score can serve as a robust prognostic tool for GC, which can effectively perform patient risk stratification and predict treatment response, providing potential value for guiding individualised treatment strategies.