ANRGs impact on gastric cancer progression and drug efficacy: A comprehensive study

Gastric cancer (GC) is a significant contributor to cancer-related mortality globally, with the heterogeneity of metastasis and treatment impacting patient prognosis. Currently, the treatment of GC still relies on early surgical resection, and comprehensive treatment is needed for patients with metastatic GC. Anikis-related genes (ANRGs) have been shown to affect tumor metastasis. Exploring the role of ANRGs in GC will help us understand the mechanism of tumor metastasis; screening precise targets and selecting appropriate chemotherapeutics will help individualize the treatment of GC patients. In this study, we established a prognostic scoring model based on ANRGs and explored their association with GC patient prognosis, immune microenvironment, chemotherapeutic drug sensitivity, and small molecule compounds. Our findings revealed that a gene signature composed of ANXA5, CCN1, EGF, VTN, and ZBTB7A accurately predicted GC patient prognosis. Patients in the low-risk group had better outcomes, higher macrophage M1 infiltration, and higher tumor mutation burden. The half maximal inhibitory concentration (IC50) values of Ponatinib (ap.24534), Motesanib (amg.706), and Navitoclax (abt.263) were lower in the high-risk group, indicating that patients in the high-risk group were more sensitive to these chemotherapy drugs, meaning with better clinical outcomes. In addition, we screened the small molecule compound SGC-CBP30 that can inhibit ANXA5 and CCN1, and these results help individualized treatment of GC patients. Our study identified key genes based on ANRGs and developed a novel gene signature for predicting the prognosis of GC patients and understanding the relationship between immunity and tumor mutation burden. Additionally, we identified chemotherapeutic drugs that can guide GC treatment and elucidated the binding affinity between specific targeted drugs and distinct protein sites, providing novel insights for the precise treatment of GC patients.