不同基因分型乳腺癌中Caspase-3、XIAP、Smac表达情况及与临床病理参数的关系

摘要

目的 探讨天冬氨酸酶3 (Caspase-3)、X连锁凋亡抑制蛋白 (XIAP)、第二个线粒体衍生半胱氨酸蛋白酶激动剂 (Smac) 在不同基因分型乳腺癌中表达情况, 及其与乳腺癌临床病理参数的相关性.方法 选取行手术切除治疗的73例乳腺癌患者为研究对象, 其中Luminal A型30例, Luminal B型12例, HER-2过表达型9例, BLBC型22例, 同期取20例癌旁正常乳腺组织作为对照组, 采用免疫组织化学 (SP) 方法检测乳腺组织中Caspase-3、XIAP、Smac蛋白表达情况, 分析三者在不同基因分型乳腺癌中表达水平及其与乳腺癌病理参数的相关性.结果 乳腺癌组织中Caspase-3蛋白阳性表达率为39.73％ (29/73), 明显低于癌旁正常乳腺组织Caspase-3蛋白阳性表达率90.00％ (18/20), 差异有统计学意义 (P＜0.05) .乳腺癌组织中XIAP蛋白阳性表达率为86.30％ (63/73), 明显高于癌旁正常乳腺组织XIAP蛋白阳性表达率40.00％ (8/20) (P＜0.05) .乳腺癌组织中Smac蛋白阳性表达率为31.51％ (23/73), 明显低于癌旁正常乳腺组织Smac蛋白阳性表达率95.00％ (19/20) (P＜0.05) .Caspase-3、XIAP、Smac蛋白表达在Luminal A型、HER-2过表达型、BLBC型之间两两比较, 差异均有统计学意义 (P＜0.05) .Caspase-3、XIAP、Smac蛋白表达与乳腺癌患者年龄、肿瘤大小、绝经情况无关 (P＞0.05), 与TNM分期、分化程度、淋巴结转移有关 (P＜0.05) .Spearman相关性分析结果显示, 乳腺癌组织中Caspase-3与XIAP蛋白表达呈明显负相关 (γ=-0.796, P＜0.01), 与Smac蛋白表达呈明显正相关 (γ=0.803, P＜0.01), XIAP与Smac蛋白表达呈明显负相关 (γ=-0.712, P＜0.01) .结论 Caspase-3、Smac蛋白在乳腺癌组织中明显低表达, XIAP蛋白呈明显高表达, 三者与乳腺癌基因分型、发生发展密切相关.%Objective To explore aspartic acid enzyme 3 (Caspase-3), X linked apoptosis inhibitory protein (XIAP), the second mitochondrial derived cysteine protease agonists (Smac) expression of breast cancer in different genotypes and the relationship with clinicopathological parameters.Methods73 cases of patients with breast cancer treated were selected as the study group, including 30 cases in Luminal type A, 12 cases in Luminal type B and 9 cases in HER-2 overexpression, and 22 cases in type BLBC.20 cases of normal breast tissue adjacent to cancer in the same period were selected as the control group.Caspase-3, XIAP and Smac proteins expression in breast tissues was detected by using Immunohistochemistry (SP) method, and the three expression in different genotypes of breast cancer and the correlation with pathological parameters of breast cancer were analyzed.Results Positive rate of Caspase-3 protein expression in breast cancer was 39.73％ (29/73), significantly lower than that of90.00％ (18/20) in normal breast tissues adjacent to breast cancer, with statistically significant difference (P＜0.05).Positive rate of XIAP protein expression in breast cancer tissues was 86.30％ (63/73), significantly higher than that of 40.00％ (8/20) in normal breast tissues adjacent to cancer (P＜0.05).The positive rate of Smac protein expression in breast cancer tissues was31.51％ (23/73), lower than that of 95.00％ (19/20) in normal breast tissues adjacent to cancer (P＜0.05).There was statistically significant difference in Caspase-3, XIAP and Smac protein expression in Luminal A group, HER-2 overexpression group, BLBC type 2 group (P＜0.05).Caspase-3, XIAP and Smac protein expression was independent of breast cancer age, tumor size, and menopa usal status (P＞0.05), and related to TNM staging, differentiation and lymph node metastasis (P＜0.05).Spearman correlation analysis showed Caspase-3 in breast cancer tissue was negatively related to XIAP protein expression (γ=-0.796, P＜0.01), ignificant positively related to Smac protein expression (γ=0.803, P＜0.01), and XIAP and Smac protein expression was negatively correlated (γ=-0.712, P＜0.01).ConclusionCaspase-3 and Smac proteins are significant low-expression in breast cancer tissues, and XIAP protein high expression.The three are closely related to the genotype and development of breast cancer.