纤维连接蛋白1在乳腺癌中的表达及其与人类表皮生长因子受体2的相关性研究

Expression and clinical significance of fibronectin 1 in breast cancer and its correlation with human epidermal growth factor receptor 2

目的 研究乳腺癌中纤维连接蛋白1(FN1)的表达及其与人类表皮生长因子受体2(HER2)表达的相关性和意义。方法 通过细胞实验探究HER2过表达细胞与HER2阴性对照组之间FN1的表达差异。通过Transwell实验检测其迁移侵袭能力;采用生物信息学方法分析FN1在乳腺癌中的表达及其与HER2表达的相关性;R语言分析FN1对乳腺癌患者总生存期和无复发生存期的影响;从GEO数据库中分析FN1与HER2阳性乳腺癌患者赫赛汀药物疗效的关系。结果 细胞实验表明,相比于HER2阴性对照组,HER2过表达细胞FN1的表达显著升高(t=8.660,P=0.000 5),且迁移侵袭能力更强(t=25.84、28.38,均P<0.001)。生物信息学分析显示,FN1在乳腺癌组织中的表达较正常组织中显著升高(P<0.001);在HER2阳性乳腺癌中表达显著高于HER2阴性乳腺癌(t=6.166,P<0.001),且与HER2的表达呈正相关(P=0.000 2)。HER2阴性乳腺癌中,FN1高表达时患者总生存期和无复发生存期缩短;而在HER2阳性乳腺癌中,FN1可作为赫赛汀新辅助治疗效果的预测因子。结论 FN1与乳腺癌HER2的表达呈正相关性。在HER2阴性乳腺癌中,FN1的表达对预测患者的生存预后具有重要意义;在HER2阳性乳腺癌新辅助治疗中,FN1对赫赛汀药物的疗效具有预测价值。

Objective To investigate the correlation between fibronectin 1(FN1)and human epidermal growth factor receptor 2(HER2)expression in breast cancer and its significance.Methods FN1 expression and invasion ability in HER2-overexpression cells and HER2-negative cells were investigated by RT-PCR and Transwell analysis,respectively.Bioinformatics analysis was carried out for the expression and the correlation between FN1 and HER2 in patients with breast cancer,while R language analysis of the effects of FN1 on the overall survival and the relapse free survival of patients with breast cancer.Results The expression of FN1 was significantly increased in HER2-overexpression cells(t=8.660,P=0.0005),and the migration and invasion ability were stronger than those in HER2-negative cells(t=25.84,28.38,both P<0.001).Bioinformatics analysis showed that the expression of FN1 in breast cancer tissues was significantly higher than that in normal tissues(P<0.001).In breast cancer tissues,the expression of FN1 was significantly higher in HER2-positive breast cancer than that in HER2-negative breast cancer(t=6.166,P<0.001),and was positively correlated with HER2 expression(P=0.0002).In HER2-negative breast cancer,high expression of FN1 was associated with a shortened overall survival and the relapse free survival.In HER2-positive breast cancer,FN1 could be used as a predictor of the efficacy of neoadjuvant therapy with herceptin.Conclusions There is positive correlation between FN1 and the expression of HER2 in breast cancer.In patients with HER2-negative breast cancer,the expression of FN1 is of great significance in predicting the survival prognosis.In neoadjuvant therapy with herceptin for HER2-positive breast cancer,FN1 has predictive value for the efficacy of herceptin.