Abstract: Objective To investigate the expression of AHNAK in the patients with gastric cancer (GC), and to analyze the relationship between AHNAK and infiltration of immune cells, especially macrophages, and to evaluate the value of AHNAK in predicting the prognosis of GC patients. Methods The data were collected from UALCAN database.The expression of AHNAK in GC tissues and normal tissues were compared, and the expression of AHNAK was analyzed among the GC patients with different age. The relationship of AHNAK expression with the levels of immune cell infiltration and its molecular markers was analyzed by TIMER 2.0. Kaplan-Meier curve was drawn to analyze the relationship of AHNAK expression and immune cell level with overall survival (OS) of the GC patients. The influencing factors of the prognosis of GC patients were analyzed by Cox regression analysis. RMS package was used to construct the nomogram of survival probability prediction, and perform the calibration analysis and visualization of the model. Results Compared with normal tissues, the expression of AHNAK was lower in GC tissues, especially in the very old patients with GC. Kaplan-Meier survival analysis showed that the level of OS in the low AHNAK expression group was lower than that in the high AHNAK expression group (P<0.01). Immunoinfiltration analysis showed that AHNAK expression was correlated with the levels of macrophages, neutrophils, dendritic cells, B cells, CD4⁺ T cells and CD8⁺ T cell infiltration. In addition, GC patients with high level of macrophage infiltration had shorter OS (P<0.01). AHNAK expression was mainly correlated with the level of M2-type macrophage (r=0.173, P<0.001). Multivariate Cox regression analysis showed that age>65 years old, low AHNAK expression and high NM stage were the independent risk factors for poor prognosis in GC patients. The nomogram for predicting survival probability of GC patients based on N stage, M stage, age and the expression of AHNAK had a good accuracy. Conclusions The expression of AHNAK is significantly down-regulated in GC patients, especially in the very old patients. AHNAK is associated with macrophage infiltration and can be used as a biomarker to predict poor prognosis in the elderly patients with GC.

Key words: gastric cancer, AHNAK, prognosis, immune cell infiltration