Objective: To explore association of the expression levels of adenylate cyclase-associated protein 2 (CAP2) in gastric cancer tissues with the histopathology and long-term prognosis of the malignancy.
Methods: This study was conducted among a total of 105 patients with gastric cancer undergoing radical gastrectomy in our hospital between January, 2010 and October, 2013. Immunohistochemistry was used to quantitatively assess the expression of CAP2 in gastric cancer tissues and the adjacent tissues. Based on the median relative expression level of CAP2 of 3.5, the patients were divided into low CAP2 expression group (n=52) and high CAP2 expression group (n=53). The Cox regression model was used to analyze the effect of CAP2 expression on the 5-year survival rate of the patients, and ROC curve analysis was used to assess the predictive value of CAP2 expression for the patients' long-term survival.
Results: Immunohistochemical analysis showed that the expression levels of CAP2 (P < 0.01) and Ki67 (P < 0.01) were significantly higher in gastric cancer tissues than in the adjacent tissues, and the expression level of CAP2 was positively correlated with Ki67 (P < 0.01), peripheral blood CEA (P < 0.01) and CA19-9 (P < 0.01). The percentages of patients with CEA≥5 μg/L, CA19-9≥37 kU/L, pathological grade of G3-G4, T stage of 3-4, and N stage of 2-3 were significantly higher in patients with high CAP2 expression than in those with low CAP2 expression (P < 0.05). Kaplan- Meier survival analysis showed that the 5-year survival rate was significantly lower in patients with a high CAP2 expression (P < 0.01). A high expression level of CAP2, CEA≥5μg/L, CA19-9≥37 and pathological grades G3-G4 were all independent risk factors for shortened 5-year survival after radical gastrectomy (P < 0.01). With the relative expression level of 3.45 as the cut-off value, the sensitivity of CAP2 was 70.15% for predicting death 5 years after the surgery, with a specificity of 71.05% and an area under the curve of 0.779 (P < 0.01).
Conclusions: CAP2 is highly expressed in gastric cancer tissues in close relation with the tumor progression. CAP2 is an independent risk factor for 5-year survival rate after radical gastrectomy for gastric cancer and can be of clinical value in prognostic evaluation of the patients.
目的: 探索腺苷酸环化酶相关蛋白2（CAP2）在胃癌组织中的表达情况，并明确其与病理组织学和远期预后的关系。
方法: 纳入105例2010年1月~2013年10月在我院接受胃癌根治术的患者，采用免疫组化法评估CAP2的表达在胃癌组织和癌旁组织中的差异，以目标蛋白相对积分光密度值量化免疫组化结果，并进一步评估CAP2与病理组织学参数的关系。以CAP2相对表达量的中位数（3.5）为界将患者分为CAP2低表达组（n=52）和高表达组（n=53），并进一步采用Cox回归模型分析CAP2表达量是否影响胃癌患者术后5年生存率。采用ROC曲线分析CPA2表达量是否对胃癌术后远期生存期具有预测价值。
结果: 免疫组化分析显示CAP2及Ki67表达量均高于癌旁组织（P < 0.01）；相关性分析显示胃癌组织CAP2表达量与Ki67、外周血CEA及CA19-9间均存在正相关关系（P < 0.01）。CAP2高表达组患者CEA≥5μg/L、CA19-9≥37 kU/L、病理分级为G3~G4、T分期为3~4期及N分期为2~3期的比例高于CAP2低表达组（P < 0.05）。K-M生存分析显示，CAP2高表达组患者术后5年生存率低于低表达组（P < 0.01）。经单因素及Cox多元回归模型分析得出，CAP2高表达、CEA≥5μg/L、CA19-9≥37 kU/L及病理分级为G3~G4为影响胃癌根治术后5年生存期的独立危险因素。此外，以CAP2相对表达量3.45为截点值，预判术后5年死亡的敏感性为70.15%，特异性为71.05%，曲线下面积为0.779（P < 0.01）。
结论: CAP2在胃癌组织中高表达并与肿瘤进展密切相关，是胃癌根治术后5年生存率的独立危险因素，对预后评估具有一定临床价值。
Keywords: adenylate cyclase-associated protein 2; gastric cancer; pathology; risk factor analysis; survival analysis.