CC3/TIP30蛋白在乳腺癌中的表达及其与HER-2/neu基因的相关性研究

目的 分析CC3/TIP30蛋白在乳腺癌中的表达及临床意义,并探讨CC3/TIP30与HER-2/neu的mRNA相关性.方法 采用免疫组化EnVision二步法检测2004年1月至2005年1月手术治疗并病理证实的112例乳腺癌标本中CC3/TIP30、HER-2/neu蛋白的表达,分析其表达与临床病理特征及预后的相关性,同时应用化学合成靶向敲除CC3/TIP30 mRNA的siRNA,并转染SK-BR-3细胞株48 h后,应用real-time PCR法测定CC3/TIP30、HER-2/neu基因mRNA的表达水平.结果 免疫组化显示CC3/TIP30蛋白在乳腺癌组织中表达与TNM分期、淋巴结转移、HER-2和分子分型相关(P=0.048、0.019、0.027、0.011),而与患者年龄、肿瘤大小,以及雌激素受体和孕激素受体表达状态无关.实时定量PCR结果示CC3/TIP30 siRNA转染导致CC3/TIP30 mRNA的表达下降,同时伴随着HER-2/neu基因mRNA水平的下降,差异有统计学意义(F=56.797,F=165.101;P均=0.000).分子分型为HER-2阳性型的乳腺癌患者中CC3/TIP30蛋白表达阳性、阴性组患者5年总生存率差异有统计学意义(X2=10.732,P=0.001).结论 CC3/TIP30蛋白表达缺失与乳腺癌的发生、发展有关,提示乳腺癌患者早期发生转移复发可能,可作为HER-2阳性型乳腺癌亚组分型的指标之一.

Clinical significance of CC3/TIP30 expression in breast carcinoma and its correlation with HER-2/neu

Objective To explore the clinical significance of CC3/TIP30 protein's expression in breast carcinoma and its correlation with HER-2/neu.Methods The expression of CC3/TIP30 and HER-2/neu protein was detected in 112 breast cancer tissues which was collected from January 2004 to January 2005 by immunohistochemistry and the relationship with clinic pathological parameters and prognosis was analyzed.Small interfering RNA (siRNA) which target to knock out CC3/TIP30 were transfected into SK-BR-3 cells.Real-time PCR were used to detect the level of CC3/TIP30 and HER-2/neu mRNA.Results The results of immunohistochemistry showed CC3/TIP30 protein was correlated with TNM stage,lymph node status,HER-2 status and molecule classification ( P =0.048,0.019,0.027,0.011 ),but there was no association with age,tumor size,estrogen receptor and progesterone receptor.Real-time PCR results revealed that CC3/TIP30 siRNA down-regulation the level of its mRNA,accompanied by a decline in the expression of HER-2/neu gene mRNA,the difference was statistically significant ( F =56.797,P =0.000 ;F =165.101,P =0.000).In addition,Kaplan-Meier curves of disease-specific survival analysis showed a marked difference in the subtype of HER-2 protein positive between CC3/TIP30 positive group and negative group ( x2 =10.732,P =0.001 ).Conclusions The loss of CC3/TIP30 is related to occurrence and development in breast cancer,suggesting early onset of metastasis and recurrence.Perhaps CC3/TIP30 can be considered as a sub-typing indicator in HER-2 positive breast cancer.