胃癌病人AHNAK表达与巨噬细胞浸润及预后的相关性

Correlation of AHNAK expression with macrophage infiltration and prognosis in patients with gastric cancer

目的 探究AHNAK在胃癌(GC)病人中的表达情况,并分析AHNAK与免疫细胞尤其是巨噬细胞浸润之间的关系,探讨AHNAK预测GC病人预后的价值。方法 利用UALCAN数据库比较GC组织与正常组织AHNAK的表达差异,并分析不同年龄分组GC病人AHNAK的表达情况。使用TIMER 2.0分析AHNAK与免疫细胞浸润及其分子标记物之间的关系。通过Kaplan-Meier曲线分析AHNAK表达情况及免疫细胞水平与GC病人总生存期(OS)的关系。采用Cox回归分析GC病人预后的影响因素,使用RMS包构建生存概率预测列线图并进行校准分析与可视化。结果 与正常组织相比,AHNAK在GC样本中低表达,且AHNAK表达量在高龄老年GC病人中显著降低。Kaplan-Meier生存分析显示,AHNAK低表达组的OS较AHNAK高表达组差,差异有统计学意义(P<0.01)。免疫浸润分析显示,AHNAK表达水平与巨噬细胞、中性粒细胞、树突状细胞、B细胞、CD4^(+)T细胞、CD8^(+)T细胞浸润水平均存在相关性;此外,高巨噬细胞浸润水平的GC病人的OS更短(P<0.01),AHNAK表达水平主要与M2型巨噬细胞浸润水平呈正相关(r=0.173,P<0.001)。多因素Cox回归分析结果显示,年龄>65岁、AHNAK低表达、高NM分期为GC病人不良预后的独立危险因素。根据N分期、M分期、年龄、AHNAK表达水平构建的预测GC病人生存概率的列线图具有较好的准确性。结论 AHNAK在GC病人中表达显著下调,尤其是高龄老年GC病人。AHNAK与巨噬细胞浸润有关,可作为预测老年GC病人预后不良的生物标志物。

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.