MACC1及其靶蛋白SPON2在乳腺癌中的表达及与预后的关系

Expressions of MACC1 and target protein SPON2 in breast cancer and their correlations with prognosis

目的:探讨结肠癌转移相关基因1(metastasis-associated in colon cancer 1,MACC1)及其靶蛋白SPON2在乳腺癌组织中的表达及与临床病理因素的相关性,并评估它们对乳腺癌患者预后的影响。方法:收集2011年1月至2011年12月间于同济医院行乳腺癌根治术的126例乳腺癌患者的癌和相应癌旁组织石蜡标本,应用免疫组化Envision法检测MACC1和SPON2蛋白在癌及癌旁组织中的表达,分析MACC1和SPON2表达与乳腺癌临床病理特征及患者预后的关系。结果:MACC1主要定位于细胞质及细胞膜,SPON2在细胞膜、细胞质及细胞外基质中出现表达,MACC1和SPON2蛋白在乳腺癌组织中的表达均明显高于癌旁组织(68. 3%vs 21. 4%和71. 4%vs 17. 5%,P均<0. 01)。MACC1表达与乳腺癌患者组织学分级、TNM分期、淋巴结转移、肿瘤复发显著相关(P均<0. 05); SPON2表达与患者TNM分期、淋巴结转移、Nottingham预后指数、肿瘤复发显著相关(P均<0. 05);二者均与ER、PR及HER2状态无关(P> 0. 05),且乳腺癌组织中MACC1和SPON2的表达呈显著正相关(P <0. 001)。Kaplan-Meier生存曲线显示,MACC1和SPON2高表达的患者总生存期(OS)和无进展生存期(PFS)均较短(P均<0. 001); Cox比例风险模型分析表明,MACC1和SPON2过表达是乳腺癌患者预后的独立影响因素(P均<0. 001)。结论:MACC1和SPON2可能参与了乳腺癌的发生、发展,在乳腺癌预后评估中具有一定价值,可能成为潜在的靶点为乳腺癌治疗提供一些新的思路。

Objective： To investigate the correlations of MACC1 and SPON2 expressions with prognosis of breast cancer patients. Methods： 126 cases of breast cancer tissues and paired para-cancerous tissues were collected in Tongji Hospital from January 2011 to December 2011. MACC1 and SPON2 expressions in breast cancer and paired para-cancerous tissues were detected by Envision immunohistochemistry. Their correlations with patients＇ clinicopathological features and postoperative survival rate were also analyzed. Results： MACC1 expression was predominantly localized in the cytoplasm and membrane,while SPON2 was localized in membranous,cytoplasmic and extracellular matrix. Higher MACC1 and SPON2 expressions were found in breast cancer tissues compared with paired para-cancerous tissues（ 68. 3% vs 21. 4%,71. 4% vs 17. 5%,P〈0. 01）. MACC1 expression was significantly correlated with patients＇ histological grade,TNM stage,lymph node metastasis and tumor recurrence（ P〈0.05）. SPON2 expression was significantly correlated with TNM stage,lymph node metastasis,Nottingham prognostic index and tumor recurrence（ P〈0. 05）. There was no significant correlation between MACC1 or SPON2 expression and ER/PR/HER2 status（ P〉0. 05）. Using Spearmen rank correlation coefficient test,we found a significant correlation between MACC1 and SPON2（ P〈0. 001）. Results of Kaplan-Meier survival curve showed that patients with high MACC1 and SPON2 expression had worse OS and PFS than patients with low MACC1 and SPON2 expression（ P〈0. 001）. Finally,multivariate analysis by Cox regression confirmed that overexpression of MACC1 and SPON2 were supposed to be independent poor prognostic factors for predicting the OS and PFS of breast cancer patients（ P〈0. 001）. Conclusion： MACC1 and SPON2 are involved in the occurrence and development of breast cancer,and could therefore serve as useful molecular markers for the evaluation of prognosis of breast cancer patients,as well as represent promising targets for therapeutic approaches.