不同分子亚型乳腺癌中程序性细胞死亡4的表达及其与预后的关系

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目的探讨不同分子亚型乳腺癌中程序性细胞死亡4(PDCD4)的表达及其与预后的关系。方法收集广东省妇幼保健院乳腺科2007年1月至2009年12月期间手术切除的乳腺癌及相应的癌旁组织标本各338例,按免疫表型将其分为管腔型(199例)、HER-2阳性型(63例)及三阴型(76例),采用SP法检测不同分子亚型乳腺癌中PDCD4的表达情况,并分析其与预后的关系。用SPSS 13.0软件进行统计学分析,率的比较用卡方检验。用Kaplan-Meier法对患者的无病生存及总生存情况进行分析,用log-rank检验比较生存曲线间的差异,运用Cox分析影响各分子亚型乳腺癌生存预后的因素。结果①338例乳腺癌中PDCD4蛋白表达总阳性率为56.80%(192/338),表达缺失率为43.20%(146/338);相应癌旁正常乳腺组织中PDCD4蛋白表达总阳性率为96.44%(326/338)。其中管腔型乳腺癌中PDCD4表达阳性率明显高于HER-2阳性型(χ2=38.315,P=0.000)及三阴型(χ2=33.746,P=0.000),而HER-2阳性型及三阴型乳腺癌中PDCD4蛋白表达阳性率差异无统计学意义(χ2=0.448,P=0.503);且管腔型、HER-2阳性型及三阴型乳腺癌中PDCD4蛋白表达阳性率均分别明显低于癌旁正常组织(χ2=39.206,P=0.000;χ2=60.398,P=0.000;χ2=65.185,P=0.000)。②管腔型乳腺癌中PDCD4表达与年龄、组织学分级、T分期及N分期均有关(χ2=3.979,P=0.046;χ2=13.826,P=0.001;χ2=12.604,P=0.002;χ2=28.613,P=0.000);HER-2阳性型乳腺癌中PDCD4表达与年龄及T分期无关(χ2=0.033,P=0.856;χ2=4.258,P=0.119),而与组织学分级及N分期有关(χ2=9.972,P=0.007;χ2=13.714,P=0.003);三阴型乳腺癌中PDCD4表达与年龄及T分期无关(χ2=0.817,P=0.366;χ2=0.990,P=0.610),而与组织学分级及N分期有关(χ2=14.269,P=0.001;χ2=7.945,P=0.047)。③338例乳腺癌中PDCD4蛋白阳性表达者其无病生存及总生存均明显优于PDCD4蛋白阴性表达者(P=0.000,P=0.000),且在各分子亚型乳腺癌中,同样显示出PDCD4蛋白阳性表达者其无病生存及总生存明显优于PDCD4蛋白阴性表达者(P=0.000,P=0.000)。④多因素分析显示,影响乳腺癌无病生存的独立因素包括T分期、N分期及PDCD4表达(P=0.004,P=0.001,P=0.000),影响乳腺癌总生存的独立因素包括组织学分级、T分期、N分期及PDCD4表达。结论 PDCD4在乳腺癌中表达下调,其中三阴型及HER-2阳性型乳腺癌中下调更明显;PDCD4蛋白阳性表达者无病生存及总生存均明显优于PDCD4蛋白阴性表达者,PDCD4可作为预测乳腺癌预后的独立因素。 Objective To investigate the expression of programmed cell death 4 (PDCD4) in different molecular subtypes of breast cancer and its relationship with prognosis. Methods A total of 338 cases of breast cancer and corresponding paracancerous tissues were collected from Department of Mammary Surgery, Guangdong Maternal and Child Health Hospital from January 2007 to December 2009. According to the immunophenotype, they were divided into luminal types (199 cases). , HER-2 positive (63 cases) and triple negative (76 cases), using SP method to detect PDCD4 expression in different molecular subtypes of breast cancer, and analyze its relationship with prognosis. SPSS 13.0 software was used for statistical analysis and the rate was compared using a chi-square test. Kaplan-Meier method was used to analyze the disease-free survival and overall survival of patients. Log-rank test was used to compare the difference between survival curves. Cox was used to analyze the factors affecting the survival of each subtype of breast cancer. Results The total positive rate of PDCD4 protein in 1338 breast cancers was 56.80% (192/338), and the missing rate was 43.20% (146/338). The total positive rate of PDCD4 protein expression in corresponding normal breast tissue was 96.44% ( 326/338). The positive rate of PDCD4 expression in luminal type breast cancer was significantly higher than HER-2 positive (χ2=38.315, P=0.000) and triple negative (χ2=33.746, P=0.000), while HER-2 positive and III. There was no significant difference in the positive rate of PDCD4 protein expression in the breast cancer (阴2=0.448, P=0.503), and the positive rates of PDCD4 protein expression in the luminal, HER-2 positive and triple negative breast cancers were significantly different. Less than normal tissue adjacent to cancer (χ2=39.206, P=0.000; χ2=60.398, P=0.000; χ2=65.185, P=0.000). PDCD4 expression in luminal type breast cancer was related to age, histological grade, T stage and N stage (χ2=3.979, P=0.046; χ2=13.826, P=0.001; χ2=12.604, P=0.002; χ2= 28.613, P=0.000); PDCD4 expression in HER-2 positive breast cancer was not associated with age and T stage (χ2=0.033, P=0.856; χ2=4.258, P=0.119), but was related to histological grading and N staging. (χ2=9.972, P=0.007; χ2=13.714, P=0.003); PDCD4 expression in triple negative breast cancer was not associated with age and T stage (χ2=0.817, P=0.366; χ2=0.990, P=0.610). It was associated with histological grade and N stage (χ2=14.269, P=0.001; χ2=7.945, P=0.047). The disease-free survival and overall survival of patients with PDCD4 protein expression in 3338 cases of breast cancer were significantly better than those with PDCD4 protein negative expression (P=0.000, P=0.000). PDCD4 also showed in all molecular subtypes of breast cancer. The disease-free survival and overall survival of those with positive protein expression were significantly better than those with negative PDCD4 protein expression (P=0.000, P=0.000). 4 Multivariate analysis showed that the independent factors affecting the disease-free survival of breast cancer included T stage, N stage, and PDCD4 expression (P=0.004, P=0.001, P=0.000). The independent factors affecting breast cancer overall survival included histological grade. , T stage, N stage, and PDCD4 expression. Conclusion The expression of PDCD4 is down-regulated in breast cancer. Down-regulation is more obvious in triple-negative and HER-2 positive breast cancer. The disease-free survival and overall survival of PDCD4 protein expression are significantly better than those of PDCD4 protein negative expression. PDCD4 can be used as Independent factors predict breast cancer prognosis.
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