Abstract
Epigenetic modification is involved in tumorigenesis and cancer progression. We developed an epigenetic modification-associated molecular classification of gastric cancer (GC) to identify signature genes that accurately predict prognosis and the efficacy of immunotherapy. Least absolute shrinkage and selection operator and multivariate Cox regression analysis were conducted to develop an epigenetic modification-associated molecular classification. We investigated the significance of PIP4P2, an independent prognostic factor of the classification system, in predicting the prognosis and immunotherapy efficacy of patients with GC. The epigenetic modification-associated molecular classification was highly associated with the clinicopathological characteristics of patients and the existing classification of GC. PIP4P2 was highly expressed in GC tissue and tumor-associated macrophages. High PIP4P2 expression in GC tissue-induced tumor progression by activating PI3K/AKT signal transduction had a negative impact on immunotherapy efficacy. High expression of PIP4P2 in macrophages was correlated with poor prognosis in patients with GC. PIP4P2 is an independent unfavorable prognostic factor of epigenetic modification-associated molecular classification, is involved in tumorigenic progression, and is essential for assessing the prognosis and immunotherapy efficacy of GC.