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中华普通外科学文献(电子版) ›› 2023, Vol. 17 ›› Issue (03) : 203 -210. doi: 10.3877/cma.j.issn.1674-0793.2023.03.009

论著

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
余楷婷, 王东, 钟豪, 何美芳, 王菊芳()   
  1. 510006 广州,华南理工大学生物科学与工程学院
    510080 广州,中山大学附属第一医院医学检验科
    510080 广州,中山大学附属第一医院外科实验室
  • 收稿日期:2022-07-28 出版日期:2023-06-01
  • 通信作者: 王菊芳
  • 基金资助:
    广州市基础研究计划基础与应用基础研究项目(202102020028)

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

Kaiting Yu, Dong Wang, Hao Zhong, Meifang He, Jufang Wang()   

  1. School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China
    Division of Laboratory Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
    Laboratory of General Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
  • Received:2022-07-28 Published:2023-06-01
  • Corresponding author: Jufang Wang
引用本文:

余楷婷, 王东, 钟豪, 何美芳, 王菊芳. 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[J/OL]. 中华普通外科学文献(电子版), 2023, 17(03): 203-210.

Kaiting Yu, Dong Wang, Hao Zhong, Meifang He, Jufang Wang. Expression and clinical significance of fibronectin 1 in breast cancer and its correlation with human epidermal growth factor receptor 2[J/OL]. Chinese Archives of General Surgery(Electronic Edition), 2023, 17(03): 203-210.

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=0.000 5), 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=0.000 2). 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.

图1 TCGA数据库中FN1在不同肿瘤及正常组织中的表达概况 A为FNI在不同肿瘤中的表达;B为FNI在乳腺癌中的表达;**P<0.05
图2 FN1与HER2的相关性及乳腺癌患者总生存期的关系 A为FN1在HER2阴性与HER2阳性乳腺癌间的表达差异;B为FN1与HER2的相关性;C为乳腺癌和正常组织中FN1与HER2的相关性;D为乳腺癌中FN1与HER2的相关性;E为正常组织中FN1与HER2的相关性;F为FN1与HER2阳性和阴性乳腺癌患者总生存期的关系;G为FN1与HER2阴性乳腺癌患者总生存期的关系;H为FN1与HER2阳性乳腺癌患者总生存期的关系;I为FN1与HER2阳性和阴性乳腺癌患者无复发生存期的关系;J为FN1与HER2阴性乳腺癌患者无复发生存期的关系;K为FN1与HER2阳性乳腺癌患者无复发生存期的关系**P<0.05
图3 FN1与HER2相关性分析 A为病例1 HER2免疫组织化学; B为病例1 FN1免疫组织化学; C为病例2 HER2免疫组织化学; D为病例2 FN1免疫组织化学; E为FN1评分与HER2评分的相关性
图4 FN1的表达与赫赛汀疗效的关系 A为样本基本信息包括FN1的mRNA水平、HER2阴性与阳性乳腺癌、治疗方案和疗效;B为HER2阴性与HER2阳性乳腺癌FN1的表达差异;C为疗效与FN1表达的关系;D为HER2阴性与HER2阳性乳腺癌疗效与FN1的表达;E为HER2阳性乳腺癌不同治疗方案组的FN1表达;F为HER2阳性乳腺癌不同治疗方案组中疗效与FN1表达的关系  P<0.05
图5 HER2与FN1在各细胞系中的表达并检测迁移与侵袭能力 A为HER2 mRNA的表达; B为FN1 mRNA的表达; C为HER2与FN1的蛋白表达;D为231-CON和231-HER2的迁移和侵袭能力  **P<0.05
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