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成纤维细胞生长因子受体 1 通过抑制 ER 蛋白表达与他莫昔芬耐药及 ER 阳性乳腺癌不良预后相关。

FGFR1 Is Associated With Tamoxifen Resistance and Poor Prognosis of ER-Positive Breast Cancers by Suppressing ER Protein Expression.

机构信息

Department of Breast Surgery, the Affiliated Hospital of Jiangnan University, Wuxi, People's Republic of China.

Department of Internal Medicine, Huadong Sanatorium, Wuxi, People's Republic of China.

出版信息

Technol Cancer Res Treat. 2021 Jan-Dec;20:15330338211004935. doi: 10.1177/15330338211004935.

DOI:10.1177/15330338211004935
PMID:33783288
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8013883/
Abstract

Fibroblast growth factor receptor 1 (FGFR1) is widely recognized as a key player in mammary carcinogenesis and associated with the prognosis and therapeutic response of breast cancers. With the aim of investigating the correlation between FGFR1 expression and estrogen receptor (ER) and exploring the effect of FGFR1 on endocrine therapy response and ER+ breast cancer prognosis, we examined the FGFR1 protein expression among 184 ER-positive breast cancers by the immunohistochemistry (IHC) method, analyzed the association between FGFR1 expression and disease characters using the Pearson's chi-square test, and assessed the prognostic role of FGFR1 among breast cancers using Cox regression and Kaplan-Meier analyses. Moreover, assays were conducted to confirm the correlation between FGFR1 and ER expression and investigate the effect of FGFR1 on tamoxifen (TAM) sensitivity in ER breast cancer. The results showed that ER expression was negatively correlated with FGFR1 expression ( = 0.011, r = -0.221). Moreover, FGFR1 expression was one of the prognostic factors of ER-positive breast cancer (OR = 1.974, 95% CI = 1.043-3.633), and high FGFR1 expression was correlated with decreased breast cancer overall survival. In addition, knocking down inhibited cell proliferation and enhanced TAM sensitivity in TAM-resistant cells. In conclusion, we found that there was a significant negative correlation between FGFR1 and ER levels in ER breast cancers, high FGFR1 protein expression was associated with poor breast cancer prognosis, down-regulating FGFR1 could elevate ER expression and is associated with enhanced TAM sensitivity in ER breast cancers.

摘要

成纤维细胞生长因子受体 1(FGFR1)被广泛认为是乳腺癌发生的关键因素,与乳腺癌的预后和治疗反应相关。为了研究 FGFR1 表达与雌激素受体(ER)的相关性,并探讨 FGFR1 对内分泌治疗反应和 ER+乳腺癌预后的影响,我们采用免疫组织化学(IHC)方法检测了 184 例 ER 阳性乳腺癌中 FGFR1 蛋白的表达,通过 Pearson 卡方检验分析 FGFR1 表达与疾病特征之间的关联,并采用 Cox 回归和 Kaplan-Meier 分析评估 FGFR1 在乳腺癌中的预后作用。此外,还进行了实验来验证 FGFR1 与 ER 表达之间的相关性,并研究 FGFR1 对 ER 阳性乳腺癌中他莫昔芬(TAM)敏感性的影响。结果表明,ER 表达与 FGFR1 表达呈负相关(=0.011,r=-0.221)。此外,FGFR1 表达是 ER 阳性乳腺癌的预后因素之一(OR=1.974,95%CI=1.043-3.633),高 FGFR1 表达与乳腺癌总生存期降低相关。此外,敲低 FGFR1 抑制了 TAM 耐药细胞的增殖并增强了 TAM 的敏感性。总之,我们发现 ER 阳性乳腺癌中 FGFR1 和 ER 水平之间存在显著的负相关,高 FGFR1 蛋白表达与乳腺癌不良预后相关,下调 FGFR1 可上调 ER 表达,并与 ER 阳性乳腺癌中 TAM 敏感性的增强相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8f1/8013883/33d4fcf14332/10.1177_15330338211004935-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8f1/8013883/0816155f28a1/10.1177_15330338211004935-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8f1/8013883/2e94d2afd004/10.1177_15330338211004935-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8f1/8013883/db621f8d3c84/10.1177_15330338211004935-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8f1/8013883/33d4fcf14332/10.1177_15330338211004935-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8f1/8013883/0816155f28a1/10.1177_15330338211004935-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8f1/8013883/2e94d2afd004/10.1177_15330338211004935-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8f1/8013883/db621f8d3c84/10.1177_15330338211004935-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8f1/8013883/33d4fcf14332/10.1177_15330338211004935-fig4.jpg

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