背景:凋亡蛋白酶激活因子1(Apaf-1)蛋白,作为参与线粒体凋亡途径激活的因素之一,在癌症生物学中起着重要作用。Apaf-1在肿瘤细胞中的表达已被证明是下调的,对肿瘤进展有重大影响。因此,我们调查了Apaf-1蛋白在波兰人群中的表达结肠腺癌患者在根治性手术前未接受任何治疗.此外,我们评估了Apaf-1蛋白表达与临床病理因素之间的关系。分析了该蛋白的预后活性与患者5年生存率的关系。为了显示Apaf-1蛋白在细胞水平上的定位,使用免疫金标记方法。
方法:本研究使用组织病理学证实的结肠腺癌患者的结肠组织材料进行。使用Apaf-1抗体以1:600稀释进行Apaf-1蛋白的免疫组织化学表达。使用Chi2检验和Chi2Yatesa检验分析Apaf-1的免疫组织化学(IHC)表达与临床参数之间的关联。采用Kaplan-Meier分析和log-rank检验验证Apaf-1表达强度与患者5年生存率的关系。当p<0.05时,认为结果具有统计学意义。
结果:通过免疫组织化学染色在整个组织切片中评估Apaf-1的表达。39个(33.23%)样本具有强的Apaf-1蛋白表达,82个(67.77%)样本具有低表达特征。Apaf-1的高表达与肿瘤的组织学分级明显相关(p=0.001)。增殖细胞核抗原(PCNA)免疫组化表达(p=0.005),年龄(p=0.015),侵袭深度(p<0.001)和血管侵袭(p<0.001)。该蛋白高表达的患者组的5年生存率明显更高(log-rank,p<0.001)。
结论:我们可以得出结论,Apaf-1表达与结肠腺癌患者生存率降低呈正相关。
The Apoptotic protease activating factor 1 (Apaf-1) protein, as one of the factors involved in the activation of the mitochondrial apoptotic pathway, plays an important role in cancer biology. Apaf-1 expression in tumour cells has been shown to be downregulated, with significant implications for tumour progression. Hence, we investigated the expression of Apaf-1 protein in the Polish population of patients with colon adenocarcinoma without any therapy prior to radical surgery. Moreover, we assessed the relation between Apaf-1 protein expression and the clinicopathological factors. The prognostic activity of this protein was analyzed in relation to 5-year survival of patients. In order to show the localization of Apaf-1 protein at the cellular level, the immunogold labelling method was used.
The study was conducted using the colon tissue material from patients with histopathologically confirmed colon adenocarcinoma. Immunohistochemical expression of Apaf-1 protein was performed using Apaf-1 antibody at dilution 1:600. The associations between the immunohistochemistry (IHC) expression of Apaf-1 and clinical parameters were analyzed using the Chi2 test and Chi2Yatesa test. Kaplan-Meier analysis and the log-rank test were used to verify the relationship between the intensity of Apaf-1 expression and 5-year survival rate of patients. The results were considered statistically significant when p < 0.05.
Apaf-1 expression was evaluated by immunohistochemical staining in whole tissue sections. Thirty-nine (33.23%) samples had strong Apaf-1 protein expression and 82 (67.77%) samples were characterized by low expression. The high expression of Apaf-1 was clearly correlated with the histological grade of the tumour (p = 0.001), proliferating cell nuclear antigen (PCNA) immunohistochemical expression (p = 0.005), age (p = 0.015), depth of invasion (p < 0.001) and angioinvasion (p < 0.001). The 5-year survival rate was significantly higher in the group of patients with high expression of this protein (log-rank, p < 0.001).
We can conclude that Apaf-1 expression is positively correlated with reduced survival of colon adenocarcinoma patients.